RLIM促进p53乙酰化分子机制及意义
|
摘要
RLIM已知的功能是作为转录辅抑制蛋白或作为E3泛素连接酶,抑制某些LIM同源蛋白的转录,参与发育的调控。
肿瘤抑制蛋白p53翻译后修饰的一种重要形式是乙酰化,由组氨酸乙酰转移酶介导。p53去乙酰化是与乙酰化相反的过程,由组氨酸去乙酰化酶介导。MDM2能够抑制组氨酸乙酰转移酶p300/CBP及PCAF介导的p53乙酰化,也能够促进组氨酸去乙酰化酶HDAC1介导的p53去乙酰化。p53是一个转录因子,具有转录激活活性,乙酰化可以提高p53的转录激活活性。
我们发现,RLIM可以与组氨酸乙酰转移酶p300互作,促进p300介导的p53乙酰化,是一个新的能调节p53乙酰化的蛋白质。RLIM对p53乙酰化的调节是依赖于MDM2的,MDM2对p300介导的p53的乙酰化有抑制作用,RLIM可以消除这种抑制作用,从而促进p300介导的p53乙酰化。同时,MDM2可以协同HDAC1对p53去乙酰化,RLIM可以抑制MDM2对p53去乙酰化,从而促进p53乙酰化。
RLIM促进p53乙酰化依赖于MDM2这一事实让我们联系到被人乳头瘤病毒(human papillomavirus,HPV)感染的细胞,在HPV阳性的宫颈癌细胞系中病毒蛋白E6会与人蛋白E6-AP形成E6/E6-AP复合物,介导p53泛素化及降解。MDM2在正常细胞内介导p53泛素化及降解,但在HPV阳性细胞中p53的泛素化及降解完全由E6/E6-AP复合物介导。RLIM依赖于MDM2促进p53乙酰化来提高p53转录激活活性对HPV阳性细胞的意义大于对正常细胞的意义,因为正常细胞里p53转录激活活性的提高还可以依赖于MDM2介导的p53泛素化减少来实现。我们发现RLIM能够促进HPV-18阳性宫颈癌细胞系HeLa细胞内p53乙酰化,这一过程依赖于MDM2。
95%宫颈癌都感染了高危险性HPV,但是HPV的存在不足以使HPV造成的病灶恶化成为肿瘤,提示从HPV感染到宫颈癌的发生之间还存在未知的机制。p53在50%的肿瘤里突变,但是在宫颈癌中几乎没有突变。在HPV阳性的宫颈癌细胞系中p53蛋白量很低,因为E6/E6-AP复合物介导了p53泛素化及降解,尽管蛋白量低,但p53是野生型的并可以被诱导发生转录激活,导致细胞发生细胞周期抑制及凋亡。因此,p53蛋白量水平低下虽然可以从一定程度解释宫颈癌的发生,但是p53在转录激活活性上受到抑制可能也是导致宫颈癌发生的原因。
我们发现RLIM提高了HeLa细胞中p53转录激活活性,并诱导HeLa细胞凋亡。我们还发现RLIM在我们检测的7例宫颈癌组织中的6例里下调。这些结果揭示出RLIM下调可能导致HPV感染细胞中p53乙酰化受到抑制,p53转录激活活性下降,细胞不能凋亡,走向癌化。我们的工作为从HPV感染到宫颈癌发生这一过程中的未知机制提供了有益的启示。
RLIM (RING finger LIM domain-binding protein) is identified as a transcriptional co-repressor as well as an E3 ubiquitin ligase to inhibit the transcriptional activities of some LIM-hd (LIM homeodomain) proteins involved in development.
Acetylation of tumor suppressor p53 is one of the posttranslational modifications of p53, which is mediated by histone acetyltransferases (HATs). Deacetylation of p53 is the contrary process of acetylation of p53, which is mediated by histone deacetylase (HDACs). MDM2 can inhibit HATs p300/CBP and PCAF mediated p53 acetylation. MDM2 also synergizes HDAC1 to mediate the deacetylation of p53. p53 is a transcription factor with transcriptional activity. Acetylation of p53 is beneficial to p53 transcriptional activation in response to stress.
We have found that RLIM can interact with HAT p300 and promotes p300 mediated p53 acetylation. RLIM is a novel protein which can regulate p53 acetylation. The promotion of p53 acetylation by RLIM is dependent on MDM2. RLIM promotes p53 acetylation both through abrogating the inhibitory effect of MDM2 on p300-mediated acetylation of p53 and through inhibiting MDM2-mediated p53 deacetylation.
We connet human papillomavirus (HPV) infected cells with the fact that RLIM targets MDM2 to promote p53 acetylation. In HPV positive cervical cancer cell lines the protein level of p53 is low, because viral E6 protein forms complex with human E6-AP protein to mediate ubiquitination and degradation of p53. p53 ubiquitination and degradation is mediated by MDM2 in normal cells. However, in HPV positive cells the ubiquitination and degradation of p53 is mediated by E6/E6-AP complex completely. Since MDM2 is replaced by E6/E6-AP on p53 ubiquitination and degradation in HPV positive cells, the fact that RLIM targets MDM2 to promote p53 acetylation is more important for p53 activation in HPV positive cells than in HPV negative cells. We have found RLIM promotes p53 acetylation in HPV-18 positive cervical cancer derived cell line HeLa cells. And the promotion is dependent on MDM2.
95% of cervical cancer is related with HPV infection. However, the presence of HPV is not sufficient for malignant progression of HPV-containing lesions, suggesting that there are still unknown mechanisms existing in the progression from HPV infection to cervical cancer. p53 is mutated in 50% of human tumors while rarely mutated in cervical cancers. In HPV positive cervical cancer cell lines the protein level of p53 is low, because E6/E6-AP complex mediates ubiquitination and degradation of p53. However, p53 is wild type and can be induced to transactivation, leading to cell cycle arrest and apoptosis in these cells. The above suggests that both low protein level of p53 and inhibition of transcriptional activity of p53 may contribute to cervical carcinogenesis.
We have found RLIM enhances the transcriptional activity of p53 in HeLa cells and induces apoptosis of the cells. RLIM is downregulated in six out of seven cervical carcinoma tissues we examined. These results indicate that downregulation of RLIM may impair the acetylation of p53 in HPV positive cells, resulting in decreasing of transcriptional activity of p53, leading to cells resistent to apoptosis and to be cancerous. Our work sheds some light in the progression from HPV infection to cervical cancer.
肿瘤抑制蛋白p53翻译后修饰的一种重要形式是乙酰化,由组氨酸乙酰转移酶介导。p53去乙酰化是与乙酰化相反的过程,由组氨酸去乙酰化酶介导。MDM2能够抑制组氨酸乙酰转移酶p300/CBP及PCAF介导的p53乙酰化,也能够促进组氨酸去乙酰化酶HDAC1介导的p53去乙酰化。p53是一个转录因子,具有转录激活活性,乙酰化可以提高p53的转录激活活性。
我们发现,RLIM可以与组氨酸乙酰转移酶p300互作,促进p300介导的p53乙酰化,是一个新的能调节p53乙酰化的蛋白质。RLIM对p53乙酰化的调节是依赖于MDM2的,MDM2对p300介导的p53的乙酰化有抑制作用,RLIM可以消除这种抑制作用,从而促进p300介导的p53乙酰化。同时,MDM2可以协同HDAC1对p53去乙酰化,RLIM可以抑制MDM2对p53去乙酰化,从而促进p53乙酰化。
RLIM促进p53乙酰化依赖于MDM2这一事实让我们联系到被人乳头瘤病毒(human papillomavirus,HPV)感染的细胞,在HPV阳性的宫颈癌细胞系中病毒蛋白E6会与人蛋白E6-AP形成E6/E6-AP复合物,介导p53泛素化及降解。MDM2在正常细胞内介导p53泛素化及降解,但在HPV阳性细胞中p53的泛素化及降解完全由E6/E6-AP复合物介导。RLIM依赖于MDM2促进p53乙酰化来提高p53转录激活活性对HPV阳性细胞的意义大于对正常细胞的意义,因为正常细胞里p53转录激活活性的提高还可以依赖于MDM2介导的p53泛素化减少来实现。我们发现RLIM能够促进HPV-18阳性宫颈癌细胞系HeLa细胞内p53乙酰化,这一过程依赖于MDM2。
95%宫颈癌都感染了高危险性HPV,但是HPV的存在不足以使HPV造成的病灶恶化成为肿瘤,提示从HPV感染到宫颈癌的发生之间还存在未知的机制。p53在50%的肿瘤里突变,但是在宫颈癌中几乎没有突变。在HPV阳性的宫颈癌细胞系中p53蛋白量很低,因为E6/E6-AP复合物介导了p53泛素化及降解,尽管蛋白量低,但p53是野生型的并可以被诱导发生转录激活,导致细胞发生细胞周期抑制及凋亡。因此,p53蛋白量水平低下虽然可以从一定程度解释宫颈癌的发生,但是p53在转录激活活性上受到抑制可能也是导致宫颈癌发生的原因。
我们发现RLIM提高了HeLa细胞中p53转录激活活性,并诱导HeLa细胞凋亡。我们还发现RLIM在我们检测的7例宫颈癌组织中的6例里下调。这些结果揭示出RLIM下调可能导致HPV感染细胞中p53乙酰化受到抑制,p53转录激活活性下降,细胞不能凋亡,走向癌化。我们的工作为从HPV感染到宫颈癌发生这一过程中的未知机制提供了有益的启示。
RLIM (RING finger LIM domain-binding protein) is identified as a transcriptional co-repressor as well as an E3 ubiquitin ligase to inhibit the transcriptional activities of some LIM-hd (LIM homeodomain) proteins involved in development.
Acetylation of tumor suppressor p53 is one of the posttranslational modifications of p53, which is mediated by histone acetyltransferases (HATs). Deacetylation of p53 is the contrary process of acetylation of p53, which is mediated by histone deacetylase (HDACs). MDM2 can inhibit HATs p300/CBP and PCAF mediated p53 acetylation. MDM2 also synergizes HDAC1 to mediate the deacetylation of p53. p53 is a transcription factor with transcriptional activity. Acetylation of p53 is beneficial to p53 transcriptional activation in response to stress.
We have found that RLIM can interact with HAT p300 and promotes p300 mediated p53 acetylation. RLIM is a novel protein which can regulate p53 acetylation. The promotion of p53 acetylation by RLIM is dependent on MDM2. RLIM promotes p53 acetylation both through abrogating the inhibitory effect of MDM2 on p300-mediated acetylation of p53 and through inhibiting MDM2-mediated p53 deacetylation.
We connet human papillomavirus (HPV) infected cells with the fact that RLIM targets MDM2 to promote p53 acetylation. In HPV positive cervical cancer cell lines the protein level of p53 is low, because viral E6 protein forms complex with human E6-AP protein to mediate ubiquitination and degradation of p53. p53 ubiquitination and degradation is mediated by MDM2 in normal cells. However, in HPV positive cells the ubiquitination and degradation of p53 is mediated by E6/E6-AP complex completely. Since MDM2 is replaced by E6/E6-AP on p53 ubiquitination and degradation in HPV positive cells, the fact that RLIM targets MDM2 to promote p53 acetylation is more important for p53 activation in HPV positive cells than in HPV negative cells. We have found RLIM promotes p53 acetylation in HPV-18 positive cervical cancer derived cell line HeLa cells. And the promotion is dependent on MDM2.
95% of cervical cancer is related with HPV infection. However, the presence of HPV is not sufficient for malignant progression of HPV-containing lesions, suggesting that there are still unknown mechanisms existing in the progression from HPV infection to cervical cancer. p53 is mutated in 50% of human tumors while rarely mutated in cervical cancers. In HPV positive cervical cancer cell lines the protein level of p53 is low, because E6/E6-AP complex mediates ubiquitination and degradation of p53. However, p53 is wild type and can be induced to transactivation, leading to cell cycle arrest and apoptosis in these cells. The above suggests that both low protein level of p53 and inhibition of transcriptional activity of p53 may contribute to cervical carcinogenesis.
We have found RLIM enhances the transcriptional activity of p53 in HeLa cells and induces apoptosis of the cells. RLIM is downregulated in six out of seven cervical carcinoma tissues we examined. These results indicate that downregulation of RLIM may impair the acetylation of p53 in HPV positive cells, resulting in decreasing of transcriptional activity of p53, leading to cells resistent to apoptosis and to be cancerous. Our work sheds some light in the progression from HPV infection to cervical cancer.
引文
章平肇,环指蛋白RLIM增强p53蛋白稳定性的分子机制研究[D].上海:复旦大学,2007:
Bach,I.(2000) The LIM domain:regulation by association[J].Mech Dev,91,5-17.
Bach,I.,Rodriguez-Esteban,C.,Carriere,C.,Bhushan,A.,Krones,A.,Rose,D.W.,Glass,C.K.,Andersen,B.,Izpisua Belmonte,J.C.and Rosenfeld,M.G.(1999) RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex[J].Nat Genet,22,394-399.
Barak,Y.,Juven,T.,Haffner,R.and Oren,M.(1993) mdm2 expression is induced by wild type p53 activity[J].Embo J,12,461-468.
Blanco,S.,Klimcakova,L.,Vega,F.M.and Lazo,P.A.(2006) The subcellular localization of vaccinia-related kinase-2(VRK2) isoforms determines their different effect on p53 stability in tumour cell lines[J].Febs J,273,2487-2504.
Bode,A.M.and Dong,Z.(2004) Post-translational modification of p53 in tumorigenesis[J].Nat Rev Cancer,4,793-805.
Brooks,C.L.and Gu,W.(2003) Ubiquitination,phosphorylation and acetylation:the molecular basis for p53 regulation[J].Curr Opin Cell Biol,15,164-171.
Butz,K.,Shahabeddin,L.,Geisen,C.,Spitkovsky,D.,Ullmann,A.and Hoppe-Seyler,F.(1995) Functional p53 protein in human papillomavirus-positive cancer cells[J].Oncogene,10,927-936.
Crook,T.,Wrede,D.,Tidy,J.A.,Mason,W.P.,Evans,D.J.and Vousden,K.H.(1992) Clonal p53 mutation in primary cervical cancer:association with human-papillomavirus-negative tumours[J].Lancet,339,1070-1073.
Crook,T.,Wrede,D.and Vousden,K.H.(1991) p53 point mutation in HPV negative human cervical carcinoma cell lines[J].Oncogene,6,873-875.
Dornan,D.,Eckert,M.,Wallace,M.,Shimizu,H.,Ramsay,E.,Hupp,T.R.and Ball,K.L.(2004) Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53[J].Mol Cell Biol,24,10083-10098.
Fang,S.,Jensen,J.P.,Ludwig,R.L.,Vousden,K.H.and Weissman,A.M.(2000)Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [J]. J Biol Chem, 275, 8945-8951.
Flores-Munguia, R., Siegel, E., Klimecki, W.T. and Giuliano, A.R. (2004) Performance assessment of eight high-throughput PCR assays for viral load quantitation of oncogenic HPV types [J]. J Mol Diagn, 6,115-124.
Gronroos, E., Terentiev, A.A., Punga, T. and Ericsson, J. (2004) YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [J].Proc Natl Acad Sci USA, 101, 12165-12170.
Grossman, S.R., Perez, M., Kung, A.L., Joseph, M., Mansur, C., Xiao, Z.X., Kumar,S., Howley, P.M. and Livingston, D.M. (1998) p300/MDM2 complexes participate in MDM2-mediated p53 degradation [J]. Mol Cell, 2,405-415.
Gu, W., Luo, J., Brooks, C.L., Nikolaev, A.Y. and Li, M. (2004) Dynamics of the p53 acetylation pathway [J]. Novartis Found Symp, 259, 197-205; discussion 205-197,223-195.
Gu, W. and Roeder, R.G. (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain [J]. Cell, 90, 595-606.
Hengstermann, A., Linares, L.K., Ciechanover, A., Whitaker, N.J. and Scheffner, M.(2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells [J]. Proc Natl Acad Sci U S A, 98,1218-1223.
Hietanen, S., Lain, S., Krausz, E., Blattner, C. and Lane, D.P. (2000) Activation of p53 in cervical carcinoma cells by small molecules [J]. Proc Natl Acad Sci U S A,97,8501-8506.
Hiratani, I., Yamamoto, N., Mochizuki, T., Ohmori, S.Y. and Taira, M. (2003) Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1 expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer functions [J]. Development, 130, 4161-4175.
Honda, R. and Yasuda, H. (2000) Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase [J]. Oncogene,19, 1473-1476.
Huang, B. H., Laban, M., Leung, C. H., Lee, L., Lee, C. K., Salto-Tellez, M., Raju,G. C. and Hooi, S. C. (2005) Inhibition of histone deacetylase 2 increases apoptosis and p21Cipl/WAF1 expression, independent of histone deacetylase 1 [J]. Cell Death Differ, 12, 395-404.
Ikenberg, H., Matthay, K., Schmitt, B., Bauknecht, T., Kiechle-Schwarz, M., Goppinger, A. and Pfleiderer, A. (1995) p53 mutation and MDM2 amplification are rare even in human papillomavirus-negative cervical carcinomas [J]. Cancer, 76, 57-66.
Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruned, G.,Viale, G., Appella, E., Pelicci, P. and Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor [J].Embo J, 23, 1144-1154.
Ito, A., Kawaguchi, Y., Lai, C.H., Kovacs, J.J., Higashimoto, Y., Appella, E. and Yao, T.P. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation [J]. Embo J, 21, 6236-6245.
Ito, A., Lai, C.H., Zhao, X., Saito, S., Hamilton, M.H., Appella, E. and Yao, T.P.(2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2 [J]. Embo J, 20, 1331-1340.
Jin, Y., Zeng, S.X., Dai, M.S., Yang, X.J. and Lu, H. (2002) MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation [J].J Biol Chem, 277, 30838-30843.
Kadrmas, J.L. and Beckerle, M.C. (2004) The LIM domain: from the cytoskeleton to the nucleus [J]. Nat Rev Mol Cell Biol, 5, 920-931.
Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y., Miura, Y., Joh, T.,Nakabayashi, H., Vaziri, H., Harris, C.C. and Riabowol, K. (2003) ING1 represses transcription by direct DNA binding and through effects on p53 [J].Cancer Res, 63, 5785-5792.
Kobayashi, T., Wang, T., Maezawa, M., Kobayashi, M., Ohnishi, S., Hatanaka, K.,Hige, S., Shimizu, Y., Kato, M., Asaka, M., Tanaka, J., Imamura, M.,Hasegawa, K., Tanaka, Y. and Brachmann, R.K. (2006) Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation [J]. Cancer Res, 66, 3137-3144.
Kobet, E., Zeng, X., Zhu, Y., Keller, D. and Lu, H. (2000) MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins [J]. Proc NatlAcadSci U S A, 97, 12547-12552.
Kramer, O.H., Zhu, P., Ostendorff, H.P., Golebiewski, M., Tiefenbach, J., Peters,M.A., Brill, B., Groner, B., Bach, I., Heinzel, T. and Gottlicher, M. (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2 [J]. Embo J, 22, 3411-3420.
Lei, Q., Jiao, J., Xin, L., Chang, C.J., Wang, S., Gao, J., Gleave, M.E., Witte, O.N.,Liu, X. and Wu, H. (2006) NKX3.1 stabilizes p53, inhibits AKT activation,and blocks prostate cancer initiation caused by PTEN loss [J]. Cancer Cell, 9,367-378.
Li, A.G., Piluso, L.G., Cai, X., Wei, G., Sellers, W.R. and Liu, X. (2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN [J].Mol Cell, 23, 575-587.
Liu, L., Scolnick, D.M., Trievel, R.C., Zhang, H.B., Marmorstein, R., Halazonetis,T.D. and Berger, S.L. (1999) p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage [J]. Mol Cell Biol, 19,1202-1209.
Luo, J., Li, M., Tang, Y., Laszkowska, M., Roeder, R.G. and Gu, W. (2004) Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo [J]. Proc Natl Acad Sci U S A, 101, 2259-2264.
Luo, J., Nikolaev, A.Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L. and Gu,W. (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress [J]. Cell, 107, 137-148.
Luo, J., Su, F., Chen, D., Shiloh, A. and Gu, W. (2000) Deacetylation of p53 modulates its effect on cell growth and apoptosis [J]. Nature, 408, 377-381.
Michael, D. and Oren, M. (2003) The p53-Mdm2 module and the ubiquitin system [J]. Semin Cancer Biol, 13, 49-58.
Miyashita, T. and Reed, J.C. (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene [J]. Cell, 80, 293-299.
Munoz, N., Bosch, F.X., Castellsague, X., Diaz, M., de Sanjose, S., Hammouda, D.,Shah, K.V. and Meijer, C.J. (2004) Against which human papillomavirus types shall we vaccinate and screen? The international perspective [J]. Int J Cancer, 111,278-285.
Nagashima, M., Shiseki, M., Miura, K., Hagiwara, K., Linke, S.P., Pedeux, R.,Wang, X.W., Yokota, J., Riabowol, K. and Harris, C.C. (2001) DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53 [J]. Proc Natl Acad Sci U S A, 98, 9671-9676.
Ostendorff, H.P., Peirano, R.I., Peters, M.A., Schluter, A., Bossenz, M., Scheffner,M. and Bach, I. (2002) Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors [J]. Nature, Vol. 416, pp. 99-103.
Pearson,M.,Carbone,R.,Sebastiani,C.,Cioce,M.,Fagioli,M.,Saito,S.,Higashimoto,Y.,Appella,E.,Minucci,S.,Pandolfi,P.P.and Pelicci,P.G.(2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras[J].Nature,406,207-210.
Pedeux,R.,Sengupta,S.,Shen,J.C.,Demidov,O.N.,Saito,S.,Onogi,H.,Kumamoto,K.,Wincovitch,S.,Garfield,S.H.,McMenamin,M.,Nagashima,M.,Grossman,S.R.,Appella,E.and Harris,C.C.(2005) ING2 regulates the onset ofreplicative senescence by induction ofp300-dependent p53acetylation[J].Mol Cell Biol,25,6639-6648.
Perry,M.E.,Piette,J.,Zawadzki,J.A.,Harvey,D.and Levine,A.J.(1993) The mdm-2 gene is induced in response to UV light in a p53-dependent manner [J].Proc Natl Acad Sci U S A,90,11623-11627.
Retaux,S.and Bachy,I.(2002) A short history of LIM domains(1993-2002):from protein interaction to degradation[J].Mol Neurobiol,26,269-281.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by avon Hippel-Lindau protein[J].Mol Cell,22,395-405.
Sakaguchi,K.,Herrera,J.E.,Saito,S.,Miki,T.,Bustin,M.,Vassilev,A.,Anderson,C.W.and Appella,E.(1998) DNA damage activates p53 through a phosphorylation-acetylation cascade[J].Genes Dev,12,2831-2841.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Scheffner,M.,Munger,K.,Byrne,J.C.and Howley,P.M.(1991) The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines[J].Proc Natl Acad Sci U S A,88,5523-5527.
Scheffner,M.and Whitaker,N.J.(2003) Human papillomavims-induced carcinogenesis and the ubiquitin-proteasome system[J].Semin Cancer Biol,13,59-67.
Skowyra,D.,Zeremski,M.,Neznanov,N.,Li,M.,Choi,Y.,Uesugi,M.,Hauser,C.A.,Gu,W.,Gudkov,A.V.and Qin,J.(2001) Differential association of products of alternative transcripts of the candidate tumor suppressor ING1with the mSin3/HDAC1 transcriptional corepressor complex[J].J Biol Chem,276,8734-8739.
Smith,J.S.,Lindsay,L.,Hoots,B.,Keys,J.,Franceschi,S.,Winer,R.and Clifford,G.M.(2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions:a meta-analysis update[J].Int J Cancer,121,621-632.
Sykes,S.M.,Mellert,H.S.,Holbert,M.A.,Li,K.,Marmorstein,R.,Lane,W.S.and McMahon,S.B.(2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction[J].Mol Cell,24,841-851.
Tang,Y.,Luo,J.,Zhang,W.and Gu,W.(2006) Tip60-dependent acetylation of p53modulates the decision between cell-cycle arrest and apoptosis[J].Mol Cell,24,827-839.
Tommasino,M.,Accardi,R.,Caldeira,S.,Dong,W.,Malanchi,I.,Smet,A.and Zehbe,I.(2003) The role of TP53 in Cervical carcinogenesis[J].Hum Mutat,21,307-312.
Vaziri,H.,Dessain,S.K.,Ng Eaton,E.,Imai,S.I.,Frye,R.A.,Pandita,T.K.,Guarente,L.and Weinberg,R.A.(2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase[J].Cell,107,149-159.
Vieyra,D.,Loewith,R.,Scott,M.,Bonnefin,P.,Boisvert,F.M.,Cheema,P.,Pastyryeva,S.,Meijer,M.,Johnston,R.N.,Bazett-Jones,D.P.,McMahon,S.,Cole,M.D.,Young,D.and Riabowol,K.(2002) Human ING1 proteins differentially regulate histone acetylation[J].J Biol Chem,277,29832-29839.
Vigushin,D.M.and Coombes,R.C.(2002) Histone deacetylase inhibitors in cancer treatment[J].Anticancer Drugs,13,1-13.
Vogelstein,B.,Lane,D.and Levine,A.J.(2000) Surfing the p53 network[J].Nature,408,307-310.
Vousden,K.H.and Lu,X.(2002) Live or let die:the cell's response to p53[J].Nat Rev Cancer,2,594-604.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wiederschain,D.,Kawai,H.,Gu,J.,Shilatifard,A.and Yuan,Z.M.(2003)Molecular basis of p53 functional inactivation by the leukemic protein MLL-ELL[J].Mol Cell Biol,23,4230-4246.
Wiederschain,D.,Kawai,H.,Shilatifard,A.and Yuan,Z.M.(2005) Multiple mixed lineage leukemia(MLL) fusion proteins suppress p53-mediated response to DNA damage[J].J Biol Chem,280,24315-24321.
Yao,Y.L.,Yang,W.M.and Seto,E.(2001) Regulation of transcription factor YY1by acetylation and deacetylation[J].Mol Cell Biol,21,5979-5991.
Zhang,Y.and Xiong,Y.(2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF[J].Cell Growth Differ,12,175-186.
Zur Hansen,H.(1996) Papillomavirus infections--a major cause of human cancers [J].Biochim Biophys Acta,1288,F55-78.
Barlev, N.A., Liu, L., Chehab, N.H., Mansfield, K., Harris, K.G., Halazonetis, T.D.and Berger, S.L. (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases [J]. Mol Cell, 8,1243-1254.
Blanco, S., Klimcakova, L., Vega, KM. and Lazo, P.A. (2006) The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines [J]. Febs J, 273,2487-2504.
Dornan, D., Eckert, M., Wallace, M., Shimizu, H., Ramsay, E., Hupp, T.R. and Ball, K.L. (2004) Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 [J]. Mol Cell Biol, 24, 10083-10098.
Espinosa, J.M. and Emerson, B.M. (2001) Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment [J].Mol Cell, 8, 57-69.
Grossman, S.R., Deato, M.E., Brignone, C, Chan, H.M., Kung, A.L., Tagami, H.,Nakatani, Y. and Livingston, D.M. (2003) Polyubiquitination of p53 by a ubiquitin ligase activity of p300 [J]. Science, 300, 342-344.
Grossman, S.R., Perez, M., Kung, A.L., Joseph, M., Mansur, C., Xiao, Z.X., Kumar,S., Howley, P.M. and Livingston, D.M. (1998) p300/MDM2 complexes participate in MDM2-mediated p53 degradation [J]. Mol Cell, 2, 405-415.
Gu, W., Luo, J., Brooks, C.L., Nikolaev, A.Y. and Li, M. (2004) Dynamics of the p53 acetylation pathway [J]. Novartis Found Symp, 259, 197-205; discussion 205-197,223-195.
Gu, W. and Roeder, R.G. (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain [J]. Cell, 90, 595-606.
Gu, W., Shi, X.L. and Roeder, R.G. (1997) Synergistic activation of transcription by CBP and p53 [J]. Nature, 387, 819-823.
Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruneri, G, Viale,G, Appella, E., Pelicci, P. and Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor [J].Embo J, 23, 1144-1154.
Ito, A., Kawaguchi, Y., Lai, C.H., Kovacs, J.J., Higashimoto, Y., Appella, E. and Yao,T.P. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation [J]. Embo J, 21, 6236-6245.
Ito, A., Lai, C.H., Zhao, X., Saito, S., Hamilton, M.H., Appella, E. and Yao, T.P.(2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2 [J]. Embo J, 20, 1331-1340.
Jin, Y, Zeng, S.X., Dai, M.S., Yang, X.J. and Lu, H. (2002) MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation [J].J Biol Chem, 277, 30838-30843.
Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y, Miura, Y, Joh, T.,Nakabayashi, H., Vaziri, H., Harris, C.C. and Riabowol, K. (2003) ING1 represses transcription by direct DNA binding and through effects on p53 [J].Cancer Res, 63, 5785-5792.
Kawaguchi, Y, Ito, A., Appella, E. and Yao, T.P. (2006) Charge modification at multiple C-terminal lysine residues regulates p53 oligomerization and its nucleus-cytoplasm trafficking [J]. J Biol Chem, 281, 1394-1400.
Kawai, H., Nie, L., Wiederschain, D. and Yuan, Z.M. (2001) Dual role of p300 in the regulation of p53 stability [J]. J Biol Chem, 276, 45928-45932.
Knights, C.D., Catania, J., Di Giovanni, S., Muratoglu, S., Perez, R., Swartzbeck, A.,Quong, A.A., Zhang, X., Beerman, T., Pestell, R.G. and Avantaggiati, M.L.(2006) Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate [J]. J Cell Biol, 173, 533-544.
Kobayashi, T., Wang, T., Maezawa, M., Kobayashi, M., Ohnishi, S., Hatanaka, K.,Hige, S., Shimizu, Y, Kato, M., Asaka, M., Tanaka, J., Imamura, M.,Hasegawa, K., Tanaka, Y. and Brachmann, R.K. (2006) Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation[J].Cancer Res,66,3137-3144.
Kobet,E.,Zeng,X.,Zhu,Y.,Keller,D.and Lu,H.(2000) MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins[J].Proc Natl Acad Sci U S A,97,12547-12552.
Le Cam,L.,Linares,L.K.,Paul,C.,Julien,E.,Lacroix,M.,Hatchi,E.,Triboulet,R.,Bossis,G.,Shmueli,A.,Rodriguez,M.S.,Coux,O.and Sardet,C.(2006)E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation[J].Cell,127,775-788.
Lei,Q.,Jiao,J.,Xin,L.,Chang,C.J.,Wang,S.,Gao,J.,Gleave,M.E.,Witte,O.N.,Liu,X.and Wu,H.(2006) NKX3.1 stabilizes p53,inhibits AKT activation,and blocks prostate cancer initiation caused by PTEN loss[J].Cancer Cell,9,367-378.
Li,A.G.,Piluso,L.G.,Cai,X.,Wei,G.,Sellers,W.R.and Liu,X.(2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN[J].Mol Cell,23,575-587.
Li,M.,Luo,J.,Brooks,C.L.and Gu,W.(2002) Acetylation of p53 inhibits its ubiquitination by Mdm2[J].J Biol Chem,277,50607-50611.
Lill,N.L.,Grossman,S.R.,Ginsberg,D.,DeCaprio,J.and Livingston,D.M.(1997)Binding and modulation of p53 by p300/CBP coactivators[J].Nature,387,823-827.
Linares,L.K.,Kiernan,R.,Triboulet,R.,Chable-Bessia,C.,Latreille,D.,Cuvier,O.,Lacroix,M.,Le Cam,L.,Coux,O.and Benkirane,M.(2007) Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2[J].Nat Cell Biol,9,331-338.
Liu,L.,Scolnick,D.M.,Trievel,R.C.,Zhang,H.B.,Marmorstein,R.,Halazonetis,T.D.and Berger,S.L.(1999) p53 sites acetylated in vitro by PCAF and p300are acetylated in vivo in response to DNA damage[J].Mol Cell Biol,19,1202-1209.
Luo,J.,Li,M.,Tang,Y.,Laszkowska,M.,Roeder,R.G.and Gu,W.(2004)Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo[J].Proc Natl Acad Sci USA,101,2259-2264.
Luo,J.,Nikolaev,A.Y.,Imai,S.,Chen,D.,Su,F.,Shiloh,A.,Guarente,L.and Gu,W.(2001)Negative control of p53 by Sir2alpha promotes cell survival under stress[J].Cell,107,137-148.
Luo,J.,Su,F.,Chen,D.,Shiloh,A.and Gu,W.(2000) Deacetylation of p53modulates its effect on cell growth and apoptosis[J].Nature,408,377-381.
Moiseeva,O.,Mallette,F.A.,Mukhopadhyay,U.K.,Moores,A.and Ferbeyre,G.(2006) DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation[J].Mol Biol Cell,17,1583-1592.
Nagashima,M.,Shiseki,M.,Miura,K.,Hagiwara,K.,Linke,S.P.,Pedeux,.R.,Wang,X.W.,Yokota,J.,Riabowol,K.and Harris,C.C.(2001) DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53[J].Proc Natl Acad Sci U S A,98,9671-9676.
Nakazawa,M.,Aratani,S.,Hatta,M.,Araya,N.,Daitoku,H.,Kawahara,K.,Watanabe,S.,Nakamura,H.,Yoshino,S.,Fujii,R.,Fujita,H.,Fukamizu,A.,Nishioka,K.and Nakajima,T.(2002) TNFalpha induces acetylation of p53but attenuates its transcriptional activation in rheumatoid synoviocytes[J].Int J Mol Med,10,269-275.
Pearson,M.,Carbone,R.,Sebastiani,C.,Cioce,M.,Fagioli,M.,Saito,S.,Higashimoto,Y.,Appella,E.,Minucci,S.,Pandolfi,P.P.and Pelicci,P.G.(2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras[J].Nature,406,207-210.
Pedeux,R.,Sengupta,S.,Shen,J.C.,Demidov,O.N.,Saito,S.,Onogi,H.,Kumamoto,K.,Wincovitch,S.,Garfield,S.H.,McMenamin,M.,Nagashima,M.,Grossman,S.R.,Appella,E.and Harris,C.C.(2005) ING2 regulates the onset of replicative senescence by induction of p300-dependent p53acetylation[J].Mol Cell Biol,25,6639-6648.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by a von Hippel-Lindau protein[J].Mol Cell,22,395-405.
Sakaguchi,K.,Herrera,J.E.,Saito,S.,Miki,T.,Bustin,M.,Vassilev,A.,Anderson,C.W.and Appella,E.(1998) DNA damage activates p53 through a phosphorylation-acetylation cascade[J].Genes Dev,12,2831-2841.
Scolnick,D.M.,Chehab,N.H.,Stavridi,E.S.,Lien,M.C.,Caruso,L.,Moran,E.,Berger,S.L.and Halazonetis,T.D.(1997) CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein[J].Cancer Res,57,3693-3696.
Shiseki,M.,Nagashima,M.,Pedeux,R.M.,Kitahama-Shiseki,M.,Miura,K., Okamura,S.,Onogi,H.,Higashimoto,Y.,Appella,E.,Yokota,J.and Harris,C.C.(2003) p29ING4 and p28ING5 bind to p53 and p300,and enhance p53activity[J].Cancer Res,63,2373-2378.
Somasundaram,K.and El-Deiry,W.S.(1997) Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region[J].Oncogene,14,1047-1057.
Sykes,S.M.,Mellert,H.S.,Holbert,M.A.,Li,K.,Marmorstein,R.,Lane,W.S.and McMahon,S.B.(2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction[J].Mol Cell,24,841-851.
Tang,Y.,Luo,J.,Zhang,W.and Gu,W.(2006) Tip60-dependent acetylation of p53modulates the decision between cell-cycle arrest and apoptosis[J].Mol Cell,24,827-839.
Vaziri,H.,Dessain,S.K.,Ng Eaton,E.,Imai,S.I.,Frye,R.A.,Pandita,T.K.,Guarente,L.and Weinberg,R.A.(2001) hS/R2(SIRT1) functions as an NAD-dependent p53 deacetylase[J].Cell,107,149-159.
Wadgaonkar,R.and Collins,T.(1999) Murine double minute(MDM2) blocks p53-coactivator interaction,a new mechanism for inhibition of p53-dependent gene expression[J].J Biol Chem,274,13760-13767.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wang,X.,Taplick,J.,Geva,N.and Oren,M.(2004) Inhibition of p53 degradation by Mdm2 acetylation[J].FEBSLett,561,195-201.
Wang,Y.H.,Tsay,Y.G.,Tan,B.C.,Lo,W.Y.and Lee,S.C.(2003) Identification and characterization of a novel p300-mediated p53 acetylation site,lysine 305[J].J Biol Chem,278,25568-25576.
Wiederschain,D.,Kawai,H.,Gu,J.,Shilatifard,A.and Yuan,Z.M.(2003)Molecular basis of p53 functional inactivation by the leukemic protein MLL-ELL[J].Mol Cell Biol,23,4230-4246.
Wiederschain,D.,Kawai,H.,Shilatifard,A.and Yuan,Z.M.(2005) Multiple mixed lineage leukemia(MLL) fusion proteins suppress p53-mediated response to DNA damage[J].J Biol Chem,280,24315-24321.
Zeng,L.,Xiao,Q.,Margariti,A.,Zhang,Z.,Zampetaki,A.,Patel,S.,Capogrossi,M.C.,Hu,Y.and Xu,Q.(2006) HDAC3 is crucial in shear-and VEGF-induced stem cell differentiation toward endothelial cells[J].J Cell Biol,174,1059-1069.
Zeng,S.X.,Jin,Y.,Kuninger,D.T.,Rotwein,P.and Lu,H.(2003) The acetylase activity of p300 is dispensable for MDM2 stabilization[J].J Biol Chem,278,7453-7458.
Zhao,B.X.,Chen,H.Z.,Lei,N.Z.,Li,G.D.,Zhao,W.X.,Zhan,Y.Y.,Liu,B.,Lin,S.C.and Wu,Q.(2006) p53 mediates the negative regulation of MDM2 by orphan receptor TR3[J].Embo J,25,5703-5715.
Zhu,Q.,Yao,J.,Wani,G.,Wani,M.A.and Wani,A.A.(2001) Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53:evidence for the role of p300 in integrating ubiquitination and proteolysis[J].J Biol Chem,276,29695-29701.
Barak, Y., Juven, T., Haffner, R. and Oren, M. (1993) mdm2 expression is induced by wild type p53 activity [J]. Embo J, 12,461-468.
Borden, K.L. and Freemont, P.S. (1996) The RING finger domain: a recent example of a sequence-structure family [J]. Curr Opin Struct Biol, 6, 395-401.
Boutell, C. and Everett, R.D. (2003) The herpes simplex virus type 1 (HSV-1) regulatory protein ICPO interacts with and Ubiquitinates p53 [J]. J Biol Chem,278,36596-36602.
Boyd, M.T., Vlatkovic, N. and Haines, D.S. (2000) A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is suppressed by MDM2 [J]. J Biol Chem, 275, 31883-31890.
Buschmann, T., Fuchs, S.Y., Lee, C.G., Pan, Z.Q. and Ronai, Z. (2000) SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53 [J]. Cell, 101, 753-762.
Buschmann, T., Lin, Y., Aithmitti, N., Fuchs, S.Y., Lu, H., Resnick-Silverman, L.,Manfredi, J.J., Ronai, Z. and Wu, X. (2001) Stabilization and activation of p53 by the coactivator protein TAFII31 [J]. J Biol Chem, 276, 13852-13857.
Chen, D., Kon, N., Li, M., Zhang, W., Qin, J. and Gu, W. (2005) ARF-BPl/Mule Is a Critical Mediator of the ARF Tumor Suppressor [J]. Cell, 121, 1071-1083.
Chen, D., Li, M., Luo, J. and Gu, W. (2003) Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function [J]. J Biol Chem, 278, 13595-13598.
Cummins, J.M., Rago, C, Kohli, M., Kinzler, K.W., Lengauer, C. and Vogelstein, B.(2004) Tumour suppression: disruption of HAUSP gene stabilizes p53 [J].Nature, 428, 1 p following 486. Cummins, J.M. and Vogelstein, B. (2004) HAUSP is required for p53 destabilization [J]. Cell Cycle, 3, 689-692.
Dai, M.S. and Lu, H. (2004) Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5 [J]. J Biol Chem, 279,44475-44482.
Dai, M.S., Zeng, S.X., Jin, Y, Sun, X.X., David, L. and Lu, H. (2004) Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition [J]. Mol Cell Biol, 24,7654-7668.
Di Stefano, V., Blandino, G, Sacchi, A., Soddu, S. and D'Orazi, G. (2004) HIPK2 neutralizes MDM2 inhibition rescuing p53 transcriptional activity and apoptotic function [J]. Oncogene, 23, 5185-5192.
Doraan, D., Wertz, I., Shimizu, H., Arnott, D., Frantz, G.D., Dowd, P., O'Rourke, K.,Koeppen, H. and Dixit, V.M. (2004) The ubiquitin ligase COP1 is a critical negative regulator of p53 [J]. Nature, 429, 86-92.
Fang, S., Jensen, J.P., Ludwig, R.L., Vousden, K.H. and Weissman, A.M. (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [J]. J Biol Chem, 275, 8945-8951.
Fuchs, S.Y., Adler, V., Buschmann, T., Yin, Z., Wu, X., Jones, S.N. and Ronai, Z.(1998) JNK targets p53 ubiquitination and degradation in nonstressed cells [J]. Genes Dev, 12, 2658-2663.
Ghosh, M., Huang, K. and Berberich, S.J. (2003) Overexpression of Mdm2 and MdmX fusion proteins alters p53 mediated transactivation, ubiquitination,and degradation [J]. Biochemistry, 42, 2291-2299.
Goldberg, Z., Vogt Sionov, R., Berger, M., Zwang, Y, Perets, R., Van Etten, R.A.,Oren, M., Taya, Y. and Haupt, Y. (2002) Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation [J]. Embo J, 21, 3715-3727.
Gronroos, E., Terentiev, A.A., Punga, T. and Ericsson, J. (2004) YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [J].Proc Natl Acad Sci U S A, 101, 12165-12170.
Gu, J., Kawai, H., Nie, L., Kitao, H., Wiederschain, D., Jochemsen, A.G., Parant, J.,Lozano, G. and Yuan, Z.M. (2002) Mutual dependence of MDM2 and MDMX in their functional inactivation of p53 [J]. J Biol Chem, 211,19251-19254.
Harada, J.N., Shevchenko, A., Pallas, D.C. and Berk, A.J. (2002) Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery[J].J Virol,76,9194-9206.
Hengstermann,A.,Linares,L.K.,Ciechanover,A.,Whitaker,N.J.and Scheffner,M.(2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells[J].Proc Natl Acad Sci U S A,98,1218-1223.
Honda,R.,Tanaka,H.and Yasuda,H.(1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53[J].FEBS Lett,420,25-27.
Honda,R.and Yasuda,H.(1999) Association of p 19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53[J].Embo J,18,22-27.
Honda,R.and Yasuda,H.(2000) Activity of MDM2,a ubiquitin ligase,toward p53or itself is dependent on the RING finger domain of the ligase[J].Oncogene,19,1473-1476.
Ito,A.,Kawaguchi,Y.,Lai,C.H.,Kovacs,J.J.,Higashimoto,Y.,Appella,E.and Yao,T.P.(2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation[J].Embo J,21,6236-6245.
Jackson,M.W.and Berberich,S.J.(2000) MdmX protects p53 from Mdm2-mediated degradation[J].Mol Cell Biol,20,1001-1007.
Katayama,H.,Sasai,K.,Kawai,H.,Yuan,Z.M.,Bondaruk,J.,Suzuki,F.,Fujii,S.,Arlinghaus,R.B.,Czerniak,B.A.and Sen,S.(2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53[J].Nat Genet,36,55-62.
Kim,H.,Kwak,N.J.,Lee,J.Y.,Choi,B.H.,Lim,Y.,Ko,Y.J.,Kim,Y.H.,Huh,P.W.,Lee,K.H.,Rha,H.K.and Wang,Y.P.(2004) Merlin neutralizes the inhibitory effect of Mdrn2 on p53[J].J Biol Chem,279,7812-7818.
Kim,M.M.,Wiederschain,D.,Kennedy,D.,Hansen,E.and Yuan,Z.M.(2007)Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins(G3BP)[J].Oncogene,26,4209-4215.
Laine,A.and Ronai,Z.(2007) Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1[J].Oncogene,26,1477-1483.
Le Cam,L.,Linares,L.K.,Paul,C.,Julien,E.,Lacroix,M.,Hatchi,E.,Triboulet,R.,Bossis,G.,Shmueli,A.,Rodriguez,M.S.,Coux,O.and Sardet,C.(2006)E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation[J].Cell 127,775-788.
Legube,G.,Linares,L.K.,Tyteca,S.,Caron,C.,Scheffner,M.,Chevillard-Briet,M.and Trouche,D.(2004) Role of the histone acetyl transferase Tip60 in the p53 pathway[J].J Biol Chem,279,44825-44833.
Leng,R.P.,Lin,Y.,Ma,W.,Wu,H.,Lemmers,B.,Chung,S.,Parant,J.M.,Lozano,G.,Hakem,R.and Benchimol,S.(2003) Pirh2,a p53-induced ubiquitin-protein ligase,promotes p53 degradation[J].Cell,112,779-791.
Li,A.G.,Piluso,L.G.,Cai,X.,Wei,G.,Sellers,W.R.and Liu,X.(2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN[J].Mol Cell,23,575-587.
Li,L.,Liao,J.,Ruland,J.,Mak,T.W.and Cohen,S.N.(2001)A TSG101/MDM2regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control[J].Proc Natl Acad Sci U S A,98,1619-1624.
Li,M.,Brooks,C.L.,Kon,N.and Gu,W.(2004) A dynamic role of HAUSP in the p53-Mdm2 pathway[J].Mol Cell,13,879-886.
Li,M.,Brooks,C.L.,Wu-Baer,F.,Chen,D.,Baer,R.and Gu,W.(2003) Monoversus polyubiquitination:differential control of p53 fate by Mdm2[J].Science,302,1972-1975.
Li,M.,Chen,D.,Shiloh,A.,Luo,J.,Nikolaev,A.Y.,Qin,J.and Gu,W.(2002a)Deubiquitination of p53 by HAUSP is an important pathway for p53stabilization[J].Nature,416,648-653.
Li,M.,Luo,J.,Brooks,C.L.and Gu,W.(2002b) Acetylation of p53 inhibits its ubiquitination by Mdrn2.J Biol Chem,277,50607-50611.
Louria-Hayon,I.,Grossman,T.,Sionov,R.V.,Alsheich,O.,Pandolfi,P.P.and Haupt,Y.(2003) The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation[J].J Biol Chem,278,33134-33141.
Luo,J.,Su,F.,Chert,D.,Shiloh,A.and Gu,W.(2000) Deacetylation of p53modulates its effect on cell growth and apoptosis[J].Nature,408,377-381.
Marechal,V.,Elenbaas,B.,Piette,J.,Nicolas,J.C.and Levine,A.J.(1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes [J].Mol Cell Biol,14,7414-7420.
Marine,J.C.and Jochemsen,A.G.(2005) Mdmx as an essential regulator of p53activity[J].Biochem Biophys Res Commun,331,750-760.
Maya,R.,Balass,M.,Kim,S.T.,Shkedy,D.,Leal,J.F.,Shifman,O.,Moas,M.,Buschmann,T.,Ronai,Z.,Shiloh,Y.,Kastan,M.B.,Katzir,E.and Oren,M.(2001) ATM-dependent phosphorylation of Mdm2 on serine 395:role in p53activation by DNA damage[J].Genes Dev,15,1067-1077.
Mayo,L.D.and Donner,D.B.(2001) A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the.nucleus[J].Proc Natl Acad Sci U S A,98,11598-11603.
Meek,D.W.and Knippschild,U.(2003) Posttranslational modification of MDM2[J].Mol Cancer Res,1,1017-1026.
Michael,D.and Oren,M.(2003) The p53-Mdm2 module and the ubiquitin system [J].Semin Cancer Biol,13,49-58.
Moll,U.M.and Petrenko,O.(2003) The MDM2-p53 interaction[J].Mol Cancer Res,1,1001-1008.
Ogawara,Y.,Kishishita,S.,Obata,T.,Isazawa,Y.,Suzuki,T.,Tanaka,K.,Masuyama,N.and Gotoh,Y.(2002) Akt enhances Mdm2-mediated ubiquitination and degradation of p53[J].J Biol Chem,277,21843-21850.
Perry,M.E.,Piette,J.,Zawadzki,J.A.,Harvey,D.and Levine,A.J.(1993) The mdm-2 gene is induced in response to UV light in a p53-dependent manner [J].Proc Natl Acad Sci U S A,90,11623-11627.
Querido,E.,Blanchette,P.,Yan,Q.,Kamura,T.,Morrison,M.,Boivin,D.,Kaelin,W.G.,Conaway,R.C.,Conaway,J.W.and Branton,P.E.(2001) Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex[J].Genes Dev,15,3104-3117.
Rajendra,R.,Malegaonkar,D.,Pungaliya,P.,Marshall,H.,Rasheed,Z.,Brownell,J.,Liu,L.F.,Lutzker,S.,Saleem,A.and Rubin,E.H.(2004) Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53[J].J Biol Chem,279,36440-36444.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by avon Hippel-Lindau protein[J].Mol Cell,22,395-405.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Sharp,D.A.,Kratowicz,S.A.,Sank,M.J.and George,D.L.(1999) Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein[J].J Biol Chem,274,38189-38196.
Stad,R.,Little,N.A.,Xirodimas,D.P.,Frenk,R.,van der Eb,A.J.,Lane,D.P.,Saville,M.K.and Jochemsen,A.G.(2001) Mdmx stabilizes p53 and Mdm2via two distinct mechanisms[J].EMBO Rep,2,1029-1034.
Stad,R.,Ramos,Y.F.,Little,N.,Grivell,S.,Attema,J.,van Der Eb,A.J.and Jochemsen,A.G.(2000) Hdmx stabilizes Mdm2 and p53[J].JBiol Chem,275,28039-28044.
Stommel,J.M.and Wahl,G.M.(2004) Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation[J].Embo J,23,1547-1556.
Sui,G.,Affar el,B.,Shi,Y.,Brignone,C.,Wall,N.R.,Yin,P.,Donohoe,M.,Luke,M.P.,Calvo,D.and Grossman,S.R.(2004) Yin Yang 1 is a negative regulator of p53[J].Cell,117,859-872.
Tao,W.and Levine,A.J.(1999) P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2[J].Proc Natl Acad Sci U S A,96,6937-6941.
Tergaonkar,V.and Perkins,N.D.(2007) p53 and NF-kappaB crosstalk:IKKalpha tips the balance[J].Mol Cell,26,158-159.
Vogelstein,B.,Lane,D.and Levine,A.J.(2000) Surfing the p53 network[J].Nature,408,307-310.
Wang,C.and Chen,J.(2003) Phosphorylation and hspg0 binding mediate heat shock stabilization of p53[J].J Biol Chem,278,2066-2071.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wang,X.,Taplick,J.,Geva,N.and Oren,M.(2004) Inhibition of p53 degradation by Mdm2 acetylation[J].FEBS Lett,561,195-201.
Weber,J.D.,Taylor,L.J.,Roussel,M.F.,Sherr,C.J.and Bar-Sagi,D.(1999)Nucleolar Arf sequesters Mdm2 and activates p53[J].Nat Cell Biol,1,20-26.
Xirodimas,D.P.,Stephen,C.W.and Lane,D.P.(2001) Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm2-mediated degradation of p53[J].Exp Cell Res,270,66-77.
Yang,H.Y.,Wen,Y.Y.,Chen,C.H.,Lozano,G.and Lee,M.H.(2003) 14-3-3 sigma positively regulates p53 and suppresses tumor growth[J].Mol Cell Biol,23,7096-7107.
Yoon,S.Y.,Lee,Y.,Kim,J.H.,Chung,A.S.,Joo,J.H.,Kim,C.N.,Kim,N.S.,Choe,I.S.and Kim,J.W.(2005) Over-expression of human UREB1 in colorectal cancer:HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein[J].Biochem Biophys Res Commun,326,7-17.
Yu,Z.K.,Geyer,R.K.and Maki,C.G.(2000) MDM2-dependent ubiquitination of nuclear and cytoplasmic P53[J].Oncogene,19,5892-5897.
Zhang,Y.,Wolf,G.W.,Bhat,K.,Jin,A.,Allio,T.,Burkhart,W.A.and Xiong,Y.(2003) Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway[J].Mol Cell Biol,23,8902-8912.
Zhang,Y.and Xiong,Y.(2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF[J].Cell Growth Differ,12,175-186.
Zhao,Y.,Katzman,R.B.,Delmolino,L.M.,Bhat,I.,Zhang,Y.,Gurumurthy,C.B.,Germaniuk-Kurowska,A.,Reddi,H.V.,Solomon,A.,Zeng,M.S.,Kung,A.,Ma,H.,Gao,Q.,Dimri,G.,Stanculescu,A.,Miele,L.,Wu,L.,Griffin,J.D.,Wazer,D.E.,Band,H.and Band,V.(2007) The notch regulator MAML1interacts with p53 and functions asa coactivator[J].JBiol Chem,282,11969-11981.
Zhu,Q.,Yao,J.,Wani,G.,Wani,M.A.and Wani,A.A.(2001) Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53:evidence for the role of p300 in integrating ubiquitination and proteolysis[J].J Biol Chem,276,29695-29701.
Barr,E.and Tamms,G.(2007) Quadrivalent human papillomavirus vaccine[J].Clin lnfect Dis,45,609-607.
Behtash,N.and Mehrdad,N.(2006) Cervical cancer:screening and prevention[J].Asian Pac J Cancer Prev,7,683-686.
Brinkman,J.A.,Hughes,S.H.,Stone,P.,Caffrey,A.S.,Muderspach,L.I.,Roman,L.D.,Weber,J.S.and Kast,W.M.(2007) Therapeutic vaccination for HPV induced cervical cancers[J].Dis Markers,23,337-352.
Bryan,J.T.(2007) Developing an HPV vaccine to prevent cervical cancer and genital warts[J].Vaccine,25,3001-3006.
Butz,K.,Shahabeddin,L.,Geisen,C.,Spitkovsky,D.,Ullmann,A.and Hoppe-Seyler,F.(1995) Functional p53 protein in human papillomavirus-positive cancer cells[J].Oncogene,10,927-936.
Crook,T.,Wrede,D.,Tidy,J.A.,Mason,W.P.,Evans,D.J.and Vousden,K.H.(1992)Clonal p53 mutation in primary cervical cancer:association with human-papillomavirus-negative tumours[J].Lancet,339,1070-1073.
Crook,T.,Wrede,D.and Vousden,K.H.(1991) p53 point mutation in HPV negative human cervical carcinoma cell lines[J].Oncogene,6,873-875.
Cram,C.P.,Abbott,D.W.and Quade,B.J.(2003) Cervical cancer screening:from the Papanicolaou smear to the vaccine era[J].J Clin Oncol,21,224s-230s.
Doorbar,J.and Cubie,H.(2005) Molecular basis for advances in cervical screening [J].Mol Diagn,9,129-142.
Hietanen,S.,Lain,S.,Krausz,E.,Blattner,C.and Lane,D.P.(2000) Activation of p53 in cervical carcinoma cells by small molecules[J].Proc Natl Acad Sci U S A,97,8501-8506.
Ikenberg,H.,Matthay,K.,Schmitt,B.,Bauknecht,T.,Kiechle-Schwarz,M.,Goppinger,A.and Pfleiderer,A.(1995) p53 mutation and MDM2amplification are rare even in human papillomavirus-negative cervical carcinomas[J].Cancer,76,57-66.
Lin,Y.Y.,Alphs,H.,Hung,C.F.,Roden,R.B.and Wu,T.C.(2007) Vaccines against human papillomavirus[J].Front Biosci,12,246-264.
Manickam,A.,Sivanandham,M.and Tourkova,I.L.(2007) Immunological role of dendritic cells in cervical cancer[J].Adv Exp Med Biol,601,155-162.
Munoz,N.,Bosch,F.X.,Castellsague,X.,Diaz,M.,de Sanjose,S.,Hammouda,D.,Shah,K.V.and Meijer,C.J.(2004) Against which human papillomavirus types shall we vaccinate and screen? The international perspective[J].Int J Cancer,111,278-285.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Scheffner,M.,Munger,K.,Byme,J.C.and Howley,P.M.(1991) The state of the p53and retinoblastoma genes in human cervical carcinoma cell lines[J].Proc Natl Acad Sci USA,88,5523-5527.
Scheffner,M.and Whitaker,N.J.(2003) Human papillomavirus-induced carcinogenesis and the ubiquitin-proteasome system[J].Semin Cancer Biol,13,59-67.
Schmiedeskamp,M.R.and Kockler,D.R.(2006) Human papillomavirus vaccines[J].Ann Pharmacother,40,1344-1352.
Smith,J.S.,Lindsay,L.,Hoots,B.,Keys,J.,Franceschi,S.,Winer,R.and Clifford,G.M.(2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions:a meta-analysis update[J].Int J Cancer,121,621-632.
Tommasino,M.,Accardi,R.,Caldeira,S.,Dong,W.,Malanchi,I.,Smet,A.and Zehbe,I.(2003) The role of TP53 in Cervical carcinogenesis[J].Hum Murat,21,307-312.
Vousden,K.H.and Lu,X.(2002) Live or let die:the cell's response to p53[J].Nat Rev Cancer,2,594-604.
zur Hausen,H.(1996) Papillomavirus infections--a major cause of human cancers [J].Biochim Biophys Acta,1288,F55-78.
Bach,I.(2000) The LIM domain:regulation by association[J].Mech Dev,91,5-17.
Bach,I.,Rodriguez-Esteban,C.,Carriere,C.,Bhushan,A.,Krones,A.,Rose,D.W.,Glass,C.K.,Andersen,B.,Izpisua Belmonte,J.C.and Rosenfeld,M.G.(1999) RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex[J].Nat Genet,22,394-399.
Barak,Y.,Juven,T.,Haffner,R.and Oren,M.(1993) mdm2 expression is induced by wild type p53 activity[J].Embo J,12,461-468.
Blanco,S.,Klimcakova,L.,Vega,F.M.and Lazo,P.A.(2006) The subcellular localization of vaccinia-related kinase-2(VRK2) isoforms determines their different effect on p53 stability in tumour cell lines[J].Febs J,273,2487-2504.
Bode,A.M.and Dong,Z.(2004) Post-translational modification of p53 in tumorigenesis[J].Nat Rev Cancer,4,793-805.
Brooks,C.L.and Gu,W.(2003) Ubiquitination,phosphorylation and acetylation:the molecular basis for p53 regulation[J].Curr Opin Cell Biol,15,164-171.
Butz,K.,Shahabeddin,L.,Geisen,C.,Spitkovsky,D.,Ullmann,A.and Hoppe-Seyler,F.(1995) Functional p53 protein in human papillomavirus-positive cancer cells[J].Oncogene,10,927-936.
Crook,T.,Wrede,D.,Tidy,J.A.,Mason,W.P.,Evans,D.J.and Vousden,K.H.(1992) Clonal p53 mutation in primary cervical cancer:association with human-papillomavirus-negative tumours[J].Lancet,339,1070-1073.
Crook,T.,Wrede,D.and Vousden,K.H.(1991) p53 point mutation in HPV negative human cervical carcinoma cell lines[J].Oncogene,6,873-875.
Dornan,D.,Eckert,M.,Wallace,M.,Shimizu,H.,Ramsay,E.,Hupp,T.R.and Ball,K.L.(2004) Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53[J].Mol Cell Biol,24,10083-10098.
Fang,S.,Jensen,J.P.,Ludwig,R.L.,Vousden,K.H.and Weissman,A.M.(2000)Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [J]. J Biol Chem, 275, 8945-8951.
Flores-Munguia, R., Siegel, E., Klimecki, W.T. and Giuliano, A.R. (2004) Performance assessment of eight high-throughput PCR assays for viral load quantitation of oncogenic HPV types [J]. J Mol Diagn, 6,115-124.
Gronroos, E., Terentiev, A.A., Punga, T. and Ericsson, J. (2004) YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [J].Proc Natl Acad Sci USA, 101, 12165-12170.
Grossman, S.R., Perez, M., Kung, A.L., Joseph, M., Mansur, C., Xiao, Z.X., Kumar,S., Howley, P.M. and Livingston, D.M. (1998) p300/MDM2 complexes participate in MDM2-mediated p53 degradation [J]. Mol Cell, 2,405-415.
Gu, W., Luo, J., Brooks, C.L., Nikolaev, A.Y. and Li, M. (2004) Dynamics of the p53 acetylation pathway [J]. Novartis Found Symp, 259, 197-205; discussion 205-197,223-195.
Gu, W. and Roeder, R.G. (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain [J]. Cell, 90, 595-606.
Hengstermann, A., Linares, L.K., Ciechanover, A., Whitaker, N.J. and Scheffner, M.(2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells [J]. Proc Natl Acad Sci U S A, 98,1218-1223.
Hietanen, S., Lain, S., Krausz, E., Blattner, C. and Lane, D.P. (2000) Activation of p53 in cervical carcinoma cells by small molecules [J]. Proc Natl Acad Sci U S A,97,8501-8506.
Hiratani, I., Yamamoto, N., Mochizuki, T., Ohmori, S.Y. and Taira, M. (2003) Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1 expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer functions [J]. Development, 130, 4161-4175.
Honda, R. and Yasuda, H. (2000) Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase [J]. Oncogene,19, 1473-1476.
Huang, B. H., Laban, M., Leung, C. H., Lee, L., Lee, C. K., Salto-Tellez, M., Raju,G. C. and Hooi, S. C. (2005) Inhibition of histone deacetylase 2 increases apoptosis and p21Cipl/WAF1 expression, independent of histone deacetylase 1 [J]. Cell Death Differ, 12, 395-404.
Ikenberg, H., Matthay, K., Schmitt, B., Bauknecht, T., Kiechle-Schwarz, M., Goppinger, A. and Pfleiderer, A. (1995) p53 mutation and MDM2 amplification are rare even in human papillomavirus-negative cervical carcinomas [J]. Cancer, 76, 57-66.
Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruned, G.,Viale, G., Appella, E., Pelicci, P. and Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor [J].Embo J, 23, 1144-1154.
Ito, A., Kawaguchi, Y., Lai, C.H., Kovacs, J.J., Higashimoto, Y., Appella, E. and Yao, T.P. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation [J]. Embo J, 21, 6236-6245.
Ito, A., Lai, C.H., Zhao, X., Saito, S., Hamilton, M.H., Appella, E. and Yao, T.P.(2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2 [J]. Embo J, 20, 1331-1340.
Jin, Y., Zeng, S.X., Dai, M.S., Yang, X.J. and Lu, H. (2002) MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation [J].J Biol Chem, 277, 30838-30843.
Kadrmas, J.L. and Beckerle, M.C. (2004) The LIM domain: from the cytoskeleton to the nucleus [J]. Nat Rev Mol Cell Biol, 5, 920-931.
Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y., Miura, Y., Joh, T.,Nakabayashi, H., Vaziri, H., Harris, C.C. and Riabowol, K. (2003) ING1 represses transcription by direct DNA binding and through effects on p53 [J].Cancer Res, 63, 5785-5792.
Kobayashi, T., Wang, T., Maezawa, M., Kobayashi, M., Ohnishi, S., Hatanaka, K.,Hige, S., Shimizu, Y., Kato, M., Asaka, M., Tanaka, J., Imamura, M.,Hasegawa, K., Tanaka, Y. and Brachmann, R.K. (2006) Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation [J]. Cancer Res, 66, 3137-3144.
Kobet, E., Zeng, X., Zhu, Y., Keller, D. and Lu, H. (2000) MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins [J]. Proc NatlAcadSci U S A, 97, 12547-12552.
Kramer, O.H., Zhu, P., Ostendorff, H.P., Golebiewski, M., Tiefenbach, J., Peters,M.A., Brill, B., Groner, B., Bach, I., Heinzel, T. and Gottlicher, M. (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2 [J]. Embo J, 22, 3411-3420.
Lei, Q., Jiao, J., Xin, L., Chang, C.J., Wang, S., Gao, J., Gleave, M.E., Witte, O.N.,Liu, X. and Wu, H. (2006) NKX3.1 stabilizes p53, inhibits AKT activation,and blocks prostate cancer initiation caused by PTEN loss [J]. Cancer Cell, 9,367-378.
Li, A.G., Piluso, L.G., Cai, X., Wei, G., Sellers, W.R. and Liu, X. (2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN [J].Mol Cell, 23, 575-587.
Liu, L., Scolnick, D.M., Trievel, R.C., Zhang, H.B., Marmorstein, R., Halazonetis,T.D. and Berger, S.L. (1999) p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage [J]. Mol Cell Biol, 19,1202-1209.
Luo, J., Li, M., Tang, Y., Laszkowska, M., Roeder, R.G. and Gu, W. (2004) Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo [J]. Proc Natl Acad Sci U S A, 101, 2259-2264.
Luo, J., Nikolaev, A.Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L. and Gu,W. (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress [J]. Cell, 107, 137-148.
Luo, J., Su, F., Chen, D., Shiloh, A. and Gu, W. (2000) Deacetylation of p53 modulates its effect on cell growth and apoptosis [J]. Nature, 408, 377-381.
Michael, D. and Oren, M. (2003) The p53-Mdm2 module and the ubiquitin system [J]. Semin Cancer Biol, 13, 49-58.
Miyashita, T. and Reed, J.C. (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene [J]. Cell, 80, 293-299.
Munoz, N., Bosch, F.X., Castellsague, X., Diaz, M., de Sanjose, S., Hammouda, D.,Shah, K.V. and Meijer, C.J. (2004) Against which human papillomavirus types shall we vaccinate and screen? The international perspective [J]. Int J Cancer, 111,278-285.
Nagashima, M., Shiseki, M., Miura, K., Hagiwara, K., Linke, S.P., Pedeux, R.,Wang, X.W., Yokota, J., Riabowol, K. and Harris, C.C. (2001) DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53 [J]. Proc Natl Acad Sci U S A, 98, 9671-9676.
Ostendorff, H.P., Peirano, R.I., Peters, M.A., Schluter, A., Bossenz, M., Scheffner,M. and Bach, I. (2002) Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors [J]. Nature, Vol. 416, pp. 99-103.
Pearson,M.,Carbone,R.,Sebastiani,C.,Cioce,M.,Fagioli,M.,Saito,S.,Higashimoto,Y.,Appella,E.,Minucci,S.,Pandolfi,P.P.and Pelicci,P.G.(2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras[J].Nature,406,207-210.
Pedeux,R.,Sengupta,S.,Shen,J.C.,Demidov,O.N.,Saito,S.,Onogi,H.,Kumamoto,K.,Wincovitch,S.,Garfield,S.H.,McMenamin,M.,Nagashima,M.,Grossman,S.R.,Appella,E.and Harris,C.C.(2005) ING2 regulates the onset ofreplicative senescence by induction ofp300-dependent p53acetylation[J].Mol Cell Biol,25,6639-6648.
Perry,M.E.,Piette,J.,Zawadzki,J.A.,Harvey,D.and Levine,A.J.(1993) The mdm-2 gene is induced in response to UV light in a p53-dependent manner [J].Proc Natl Acad Sci U S A,90,11623-11627.
Retaux,S.and Bachy,I.(2002) A short history of LIM domains(1993-2002):from protein interaction to degradation[J].Mol Neurobiol,26,269-281.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by avon Hippel-Lindau protein[J].Mol Cell,22,395-405.
Sakaguchi,K.,Herrera,J.E.,Saito,S.,Miki,T.,Bustin,M.,Vassilev,A.,Anderson,C.W.and Appella,E.(1998) DNA damage activates p53 through a phosphorylation-acetylation cascade[J].Genes Dev,12,2831-2841.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Scheffner,M.,Munger,K.,Byrne,J.C.and Howley,P.M.(1991) The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines[J].Proc Natl Acad Sci U S A,88,5523-5527.
Scheffner,M.and Whitaker,N.J.(2003) Human papillomavims-induced carcinogenesis and the ubiquitin-proteasome system[J].Semin Cancer Biol,13,59-67.
Skowyra,D.,Zeremski,M.,Neznanov,N.,Li,M.,Choi,Y.,Uesugi,M.,Hauser,C.A.,Gu,W.,Gudkov,A.V.and Qin,J.(2001) Differential association of products of alternative transcripts of the candidate tumor suppressor ING1with the mSin3/HDAC1 transcriptional corepressor complex[J].J Biol Chem,276,8734-8739.
Smith,J.S.,Lindsay,L.,Hoots,B.,Keys,J.,Franceschi,S.,Winer,R.and Clifford,G.M.(2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions:a meta-analysis update[J].Int J Cancer,121,621-632.
Sykes,S.M.,Mellert,H.S.,Holbert,M.A.,Li,K.,Marmorstein,R.,Lane,W.S.and McMahon,S.B.(2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction[J].Mol Cell,24,841-851.
Tang,Y.,Luo,J.,Zhang,W.and Gu,W.(2006) Tip60-dependent acetylation of p53modulates the decision between cell-cycle arrest and apoptosis[J].Mol Cell,24,827-839.
Tommasino,M.,Accardi,R.,Caldeira,S.,Dong,W.,Malanchi,I.,Smet,A.and Zehbe,I.(2003) The role of TP53 in Cervical carcinogenesis[J].Hum Mutat,21,307-312.
Vaziri,H.,Dessain,S.K.,Ng Eaton,E.,Imai,S.I.,Frye,R.A.,Pandita,T.K.,Guarente,L.and Weinberg,R.A.(2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase[J].Cell,107,149-159.
Vieyra,D.,Loewith,R.,Scott,M.,Bonnefin,P.,Boisvert,F.M.,Cheema,P.,Pastyryeva,S.,Meijer,M.,Johnston,R.N.,Bazett-Jones,D.P.,McMahon,S.,Cole,M.D.,Young,D.and Riabowol,K.(2002) Human ING1 proteins differentially regulate histone acetylation[J].J Biol Chem,277,29832-29839.
Vigushin,D.M.and Coombes,R.C.(2002) Histone deacetylase inhibitors in cancer treatment[J].Anticancer Drugs,13,1-13.
Vogelstein,B.,Lane,D.and Levine,A.J.(2000) Surfing the p53 network[J].Nature,408,307-310.
Vousden,K.H.and Lu,X.(2002) Live or let die:the cell's response to p53[J].Nat Rev Cancer,2,594-604.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wiederschain,D.,Kawai,H.,Gu,J.,Shilatifard,A.and Yuan,Z.M.(2003)Molecular basis of p53 functional inactivation by the leukemic protein MLL-ELL[J].Mol Cell Biol,23,4230-4246.
Wiederschain,D.,Kawai,H.,Shilatifard,A.and Yuan,Z.M.(2005) Multiple mixed lineage leukemia(MLL) fusion proteins suppress p53-mediated response to DNA damage[J].J Biol Chem,280,24315-24321.
Yao,Y.L.,Yang,W.M.and Seto,E.(2001) Regulation of transcription factor YY1by acetylation and deacetylation[J].Mol Cell Biol,21,5979-5991.
Zhang,Y.and Xiong,Y.(2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF[J].Cell Growth Differ,12,175-186.
Zur Hansen,H.(1996) Papillomavirus infections--a major cause of human cancers [J].Biochim Biophys Acta,1288,F55-78.
Barlev, N.A., Liu, L., Chehab, N.H., Mansfield, K., Harris, K.G., Halazonetis, T.D.and Berger, S.L. (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases [J]. Mol Cell, 8,1243-1254.
Blanco, S., Klimcakova, L., Vega, KM. and Lazo, P.A. (2006) The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines [J]. Febs J, 273,2487-2504.
Dornan, D., Eckert, M., Wallace, M., Shimizu, H., Ramsay, E., Hupp, T.R. and Ball, K.L. (2004) Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 [J]. Mol Cell Biol, 24, 10083-10098.
Espinosa, J.M. and Emerson, B.M. (2001) Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment [J].Mol Cell, 8, 57-69.
Grossman, S.R., Deato, M.E., Brignone, C, Chan, H.M., Kung, A.L., Tagami, H.,Nakatani, Y. and Livingston, D.M. (2003) Polyubiquitination of p53 by a ubiquitin ligase activity of p300 [J]. Science, 300, 342-344.
Grossman, S.R., Perez, M., Kung, A.L., Joseph, M., Mansur, C., Xiao, Z.X., Kumar,S., Howley, P.M. and Livingston, D.M. (1998) p300/MDM2 complexes participate in MDM2-mediated p53 degradation [J]. Mol Cell, 2, 405-415.
Gu, W., Luo, J., Brooks, C.L., Nikolaev, A.Y. and Li, M. (2004) Dynamics of the p53 acetylation pathway [J]. Novartis Found Symp, 259, 197-205; discussion 205-197,223-195.
Gu, W. and Roeder, R.G. (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain [J]. Cell, 90, 595-606.
Gu, W., Shi, X.L. and Roeder, R.G. (1997) Synergistic activation of transcription by CBP and p53 [J]. Nature, 387, 819-823.
Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruneri, G, Viale,G, Appella, E., Pelicci, P. and Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor [J].Embo J, 23, 1144-1154.
Ito, A., Kawaguchi, Y., Lai, C.H., Kovacs, J.J., Higashimoto, Y., Appella, E. and Yao,T.P. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation [J]. Embo J, 21, 6236-6245.
Ito, A., Lai, C.H., Zhao, X., Saito, S., Hamilton, M.H., Appella, E. and Yao, T.P.(2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2 [J]. Embo J, 20, 1331-1340.
Jin, Y, Zeng, S.X., Dai, M.S., Yang, X.J. and Lu, H. (2002) MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation [J].J Biol Chem, 277, 30838-30843.
Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y, Miura, Y, Joh, T.,Nakabayashi, H., Vaziri, H., Harris, C.C. and Riabowol, K. (2003) ING1 represses transcription by direct DNA binding and through effects on p53 [J].Cancer Res, 63, 5785-5792.
Kawaguchi, Y, Ito, A., Appella, E. and Yao, T.P. (2006) Charge modification at multiple C-terminal lysine residues regulates p53 oligomerization and its nucleus-cytoplasm trafficking [J]. J Biol Chem, 281, 1394-1400.
Kawai, H., Nie, L., Wiederschain, D. and Yuan, Z.M. (2001) Dual role of p300 in the regulation of p53 stability [J]. J Biol Chem, 276, 45928-45932.
Knights, C.D., Catania, J., Di Giovanni, S., Muratoglu, S., Perez, R., Swartzbeck, A.,Quong, A.A., Zhang, X., Beerman, T., Pestell, R.G. and Avantaggiati, M.L.(2006) Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate [J]. J Cell Biol, 173, 533-544.
Kobayashi, T., Wang, T., Maezawa, M., Kobayashi, M., Ohnishi, S., Hatanaka, K.,Hige, S., Shimizu, Y, Kato, M., Asaka, M., Tanaka, J., Imamura, M.,Hasegawa, K., Tanaka, Y. and Brachmann, R.K. (2006) Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation[J].Cancer Res,66,3137-3144.
Kobet,E.,Zeng,X.,Zhu,Y.,Keller,D.and Lu,H.(2000) MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins[J].Proc Natl Acad Sci U S A,97,12547-12552.
Le Cam,L.,Linares,L.K.,Paul,C.,Julien,E.,Lacroix,M.,Hatchi,E.,Triboulet,R.,Bossis,G.,Shmueli,A.,Rodriguez,M.S.,Coux,O.and Sardet,C.(2006)E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation[J].Cell,127,775-788.
Lei,Q.,Jiao,J.,Xin,L.,Chang,C.J.,Wang,S.,Gao,J.,Gleave,M.E.,Witte,O.N.,Liu,X.and Wu,H.(2006) NKX3.1 stabilizes p53,inhibits AKT activation,and blocks prostate cancer initiation caused by PTEN loss[J].Cancer Cell,9,367-378.
Li,A.G.,Piluso,L.G.,Cai,X.,Wei,G.,Sellers,W.R.and Liu,X.(2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN[J].Mol Cell,23,575-587.
Li,M.,Luo,J.,Brooks,C.L.and Gu,W.(2002) Acetylation of p53 inhibits its ubiquitination by Mdm2[J].J Biol Chem,277,50607-50611.
Lill,N.L.,Grossman,S.R.,Ginsberg,D.,DeCaprio,J.and Livingston,D.M.(1997)Binding and modulation of p53 by p300/CBP coactivators[J].Nature,387,823-827.
Linares,L.K.,Kiernan,R.,Triboulet,R.,Chable-Bessia,C.,Latreille,D.,Cuvier,O.,Lacroix,M.,Le Cam,L.,Coux,O.and Benkirane,M.(2007) Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2[J].Nat Cell Biol,9,331-338.
Liu,L.,Scolnick,D.M.,Trievel,R.C.,Zhang,H.B.,Marmorstein,R.,Halazonetis,T.D.and Berger,S.L.(1999) p53 sites acetylated in vitro by PCAF and p300are acetylated in vivo in response to DNA damage[J].Mol Cell Biol,19,1202-1209.
Luo,J.,Li,M.,Tang,Y.,Laszkowska,M.,Roeder,R.G.and Gu,W.(2004)Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo[J].Proc Natl Acad Sci USA,101,2259-2264.
Luo,J.,Nikolaev,A.Y.,Imai,S.,Chen,D.,Su,F.,Shiloh,A.,Guarente,L.and Gu,W.(2001)Negative control of p53 by Sir2alpha promotes cell survival under stress[J].Cell,107,137-148.
Luo,J.,Su,F.,Chen,D.,Shiloh,A.and Gu,W.(2000) Deacetylation of p53modulates its effect on cell growth and apoptosis[J].Nature,408,377-381.
Moiseeva,O.,Mallette,F.A.,Mukhopadhyay,U.K.,Moores,A.and Ferbeyre,G.(2006) DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation[J].Mol Biol Cell,17,1583-1592.
Nagashima,M.,Shiseki,M.,Miura,K.,Hagiwara,K.,Linke,S.P.,Pedeux,.R.,Wang,X.W.,Yokota,J.,Riabowol,K.and Harris,C.C.(2001) DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53[J].Proc Natl Acad Sci U S A,98,9671-9676.
Nakazawa,M.,Aratani,S.,Hatta,M.,Araya,N.,Daitoku,H.,Kawahara,K.,Watanabe,S.,Nakamura,H.,Yoshino,S.,Fujii,R.,Fujita,H.,Fukamizu,A.,Nishioka,K.and Nakajima,T.(2002) TNFalpha induces acetylation of p53but attenuates its transcriptional activation in rheumatoid synoviocytes[J].Int J Mol Med,10,269-275.
Pearson,M.,Carbone,R.,Sebastiani,C.,Cioce,M.,Fagioli,M.,Saito,S.,Higashimoto,Y.,Appella,E.,Minucci,S.,Pandolfi,P.P.and Pelicci,P.G.(2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras[J].Nature,406,207-210.
Pedeux,R.,Sengupta,S.,Shen,J.C.,Demidov,O.N.,Saito,S.,Onogi,H.,Kumamoto,K.,Wincovitch,S.,Garfield,S.H.,McMenamin,M.,Nagashima,M.,Grossman,S.R.,Appella,E.and Harris,C.C.(2005) ING2 regulates the onset of replicative senescence by induction of p300-dependent p53acetylation[J].Mol Cell Biol,25,6639-6648.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by a von Hippel-Lindau protein[J].Mol Cell,22,395-405.
Sakaguchi,K.,Herrera,J.E.,Saito,S.,Miki,T.,Bustin,M.,Vassilev,A.,Anderson,C.W.and Appella,E.(1998) DNA damage activates p53 through a phosphorylation-acetylation cascade[J].Genes Dev,12,2831-2841.
Scolnick,D.M.,Chehab,N.H.,Stavridi,E.S.,Lien,M.C.,Caruso,L.,Moran,E.,Berger,S.L.and Halazonetis,T.D.(1997) CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein[J].Cancer Res,57,3693-3696.
Shiseki,M.,Nagashima,M.,Pedeux,R.M.,Kitahama-Shiseki,M.,Miura,K., Okamura,S.,Onogi,H.,Higashimoto,Y.,Appella,E.,Yokota,J.and Harris,C.C.(2003) p29ING4 and p28ING5 bind to p53 and p300,and enhance p53activity[J].Cancer Res,63,2373-2378.
Somasundaram,K.and El-Deiry,W.S.(1997) Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region[J].Oncogene,14,1047-1057.
Sykes,S.M.,Mellert,H.S.,Holbert,M.A.,Li,K.,Marmorstein,R.,Lane,W.S.and McMahon,S.B.(2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction[J].Mol Cell,24,841-851.
Tang,Y.,Luo,J.,Zhang,W.and Gu,W.(2006) Tip60-dependent acetylation of p53modulates the decision between cell-cycle arrest and apoptosis[J].Mol Cell,24,827-839.
Vaziri,H.,Dessain,S.K.,Ng Eaton,E.,Imai,S.I.,Frye,R.A.,Pandita,T.K.,Guarente,L.and Weinberg,R.A.(2001) hS/R2(SIRT1) functions as an NAD-dependent p53 deacetylase[J].Cell,107,149-159.
Wadgaonkar,R.and Collins,T.(1999) Murine double minute(MDM2) blocks p53-coactivator interaction,a new mechanism for inhibition of p53-dependent gene expression[J].J Biol Chem,274,13760-13767.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wang,X.,Taplick,J.,Geva,N.and Oren,M.(2004) Inhibition of p53 degradation by Mdm2 acetylation[J].FEBSLett,561,195-201.
Wang,Y.H.,Tsay,Y.G.,Tan,B.C.,Lo,W.Y.and Lee,S.C.(2003) Identification and characterization of a novel p300-mediated p53 acetylation site,lysine 305[J].J Biol Chem,278,25568-25576.
Wiederschain,D.,Kawai,H.,Gu,J.,Shilatifard,A.and Yuan,Z.M.(2003)Molecular basis of p53 functional inactivation by the leukemic protein MLL-ELL[J].Mol Cell Biol,23,4230-4246.
Wiederschain,D.,Kawai,H.,Shilatifard,A.and Yuan,Z.M.(2005) Multiple mixed lineage leukemia(MLL) fusion proteins suppress p53-mediated response to DNA damage[J].J Biol Chem,280,24315-24321.
Zeng,L.,Xiao,Q.,Margariti,A.,Zhang,Z.,Zampetaki,A.,Patel,S.,Capogrossi,M.C.,Hu,Y.and Xu,Q.(2006) HDAC3 is crucial in shear-and VEGF-induced stem cell differentiation toward endothelial cells[J].J Cell Biol,174,1059-1069.
Zeng,S.X.,Jin,Y.,Kuninger,D.T.,Rotwein,P.and Lu,H.(2003) The acetylase activity of p300 is dispensable for MDM2 stabilization[J].J Biol Chem,278,7453-7458.
Zhao,B.X.,Chen,H.Z.,Lei,N.Z.,Li,G.D.,Zhao,W.X.,Zhan,Y.Y.,Liu,B.,Lin,S.C.and Wu,Q.(2006) p53 mediates the negative regulation of MDM2 by orphan receptor TR3[J].Embo J,25,5703-5715.
Zhu,Q.,Yao,J.,Wani,G.,Wani,M.A.and Wani,A.A.(2001) Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53:evidence for the role of p300 in integrating ubiquitination and proteolysis[J].J Biol Chem,276,29695-29701.
Barak, Y., Juven, T., Haffner, R. and Oren, M. (1993) mdm2 expression is induced by wild type p53 activity [J]. Embo J, 12,461-468.
Borden, K.L. and Freemont, P.S. (1996) The RING finger domain: a recent example of a sequence-structure family [J]. Curr Opin Struct Biol, 6, 395-401.
Boutell, C. and Everett, R.D. (2003) The herpes simplex virus type 1 (HSV-1) regulatory protein ICPO interacts with and Ubiquitinates p53 [J]. J Biol Chem,278,36596-36602.
Boyd, M.T., Vlatkovic, N. and Haines, D.S. (2000) A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is suppressed by MDM2 [J]. J Biol Chem, 275, 31883-31890.
Buschmann, T., Fuchs, S.Y., Lee, C.G., Pan, Z.Q. and Ronai, Z. (2000) SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53 [J]. Cell, 101, 753-762.
Buschmann, T., Lin, Y., Aithmitti, N., Fuchs, S.Y., Lu, H., Resnick-Silverman, L.,Manfredi, J.J., Ronai, Z. and Wu, X. (2001) Stabilization and activation of p53 by the coactivator protein TAFII31 [J]. J Biol Chem, 276, 13852-13857.
Chen, D., Kon, N., Li, M., Zhang, W., Qin, J. and Gu, W. (2005) ARF-BPl/Mule Is a Critical Mediator of the ARF Tumor Suppressor [J]. Cell, 121, 1071-1083.
Chen, D., Li, M., Luo, J. and Gu, W. (2003) Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function [J]. J Biol Chem, 278, 13595-13598.
Cummins, J.M., Rago, C, Kohli, M., Kinzler, K.W., Lengauer, C. and Vogelstein, B.(2004) Tumour suppression: disruption of HAUSP gene stabilizes p53 [J].Nature, 428, 1 p following 486. Cummins, J.M. and Vogelstein, B. (2004) HAUSP is required for p53 destabilization [J]. Cell Cycle, 3, 689-692.
Dai, M.S. and Lu, H. (2004) Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5 [J]. J Biol Chem, 279,44475-44482.
Dai, M.S., Zeng, S.X., Jin, Y, Sun, X.X., David, L. and Lu, H. (2004) Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition [J]. Mol Cell Biol, 24,7654-7668.
Di Stefano, V., Blandino, G, Sacchi, A., Soddu, S. and D'Orazi, G. (2004) HIPK2 neutralizes MDM2 inhibition rescuing p53 transcriptional activity and apoptotic function [J]. Oncogene, 23, 5185-5192.
Doraan, D., Wertz, I., Shimizu, H., Arnott, D., Frantz, G.D., Dowd, P., O'Rourke, K.,Koeppen, H. and Dixit, V.M. (2004) The ubiquitin ligase COP1 is a critical negative regulator of p53 [J]. Nature, 429, 86-92.
Fang, S., Jensen, J.P., Ludwig, R.L., Vousden, K.H. and Weissman, A.M. (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [J]. J Biol Chem, 275, 8945-8951.
Fuchs, S.Y., Adler, V., Buschmann, T., Yin, Z., Wu, X., Jones, S.N. and Ronai, Z.(1998) JNK targets p53 ubiquitination and degradation in nonstressed cells [J]. Genes Dev, 12, 2658-2663.
Ghosh, M., Huang, K. and Berberich, S.J. (2003) Overexpression of Mdm2 and MdmX fusion proteins alters p53 mediated transactivation, ubiquitination,and degradation [J]. Biochemistry, 42, 2291-2299.
Goldberg, Z., Vogt Sionov, R., Berger, M., Zwang, Y, Perets, R., Van Etten, R.A.,Oren, M., Taya, Y. and Haupt, Y. (2002) Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation [J]. Embo J, 21, 3715-3727.
Gronroos, E., Terentiev, A.A., Punga, T. and Ericsson, J. (2004) YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [J].Proc Natl Acad Sci U S A, 101, 12165-12170.
Gu, J., Kawai, H., Nie, L., Kitao, H., Wiederschain, D., Jochemsen, A.G., Parant, J.,Lozano, G. and Yuan, Z.M. (2002) Mutual dependence of MDM2 and MDMX in their functional inactivation of p53 [J]. J Biol Chem, 211,19251-19254.
Harada, J.N., Shevchenko, A., Pallas, D.C. and Berk, A.J. (2002) Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery[J].J Virol,76,9194-9206.
Hengstermann,A.,Linares,L.K.,Ciechanover,A.,Whitaker,N.J.and Scheffner,M.(2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells[J].Proc Natl Acad Sci U S A,98,1218-1223.
Honda,R.,Tanaka,H.and Yasuda,H.(1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53[J].FEBS Lett,420,25-27.
Honda,R.and Yasuda,H.(1999) Association of p 19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53[J].Embo J,18,22-27.
Honda,R.and Yasuda,H.(2000) Activity of MDM2,a ubiquitin ligase,toward p53or itself is dependent on the RING finger domain of the ligase[J].Oncogene,19,1473-1476.
Ito,A.,Kawaguchi,Y.,Lai,C.H.,Kovacs,J.J.,Higashimoto,Y.,Appella,E.and Yao,T.P.(2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation[J].Embo J,21,6236-6245.
Jackson,M.W.and Berberich,S.J.(2000) MdmX protects p53 from Mdm2-mediated degradation[J].Mol Cell Biol,20,1001-1007.
Katayama,H.,Sasai,K.,Kawai,H.,Yuan,Z.M.,Bondaruk,J.,Suzuki,F.,Fujii,S.,Arlinghaus,R.B.,Czerniak,B.A.and Sen,S.(2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53[J].Nat Genet,36,55-62.
Kim,H.,Kwak,N.J.,Lee,J.Y.,Choi,B.H.,Lim,Y.,Ko,Y.J.,Kim,Y.H.,Huh,P.W.,Lee,K.H.,Rha,H.K.and Wang,Y.P.(2004) Merlin neutralizes the inhibitory effect of Mdrn2 on p53[J].J Biol Chem,279,7812-7818.
Kim,M.M.,Wiederschain,D.,Kennedy,D.,Hansen,E.and Yuan,Z.M.(2007)Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins(G3BP)[J].Oncogene,26,4209-4215.
Laine,A.and Ronai,Z.(2007) Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1[J].Oncogene,26,1477-1483.
Le Cam,L.,Linares,L.K.,Paul,C.,Julien,E.,Lacroix,M.,Hatchi,E.,Triboulet,R.,Bossis,G.,Shmueli,A.,Rodriguez,M.S.,Coux,O.and Sardet,C.(2006)E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation[J].Cell 127,775-788.
Legube,G.,Linares,L.K.,Tyteca,S.,Caron,C.,Scheffner,M.,Chevillard-Briet,M.and Trouche,D.(2004) Role of the histone acetyl transferase Tip60 in the p53 pathway[J].J Biol Chem,279,44825-44833.
Leng,R.P.,Lin,Y.,Ma,W.,Wu,H.,Lemmers,B.,Chung,S.,Parant,J.M.,Lozano,G.,Hakem,R.and Benchimol,S.(2003) Pirh2,a p53-induced ubiquitin-protein ligase,promotes p53 degradation[J].Cell,112,779-791.
Li,A.G.,Piluso,L.G.,Cai,X.,Wei,G.,Sellers,W.R.and Liu,X.(2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN[J].Mol Cell,23,575-587.
Li,L.,Liao,J.,Ruland,J.,Mak,T.W.and Cohen,S.N.(2001)A TSG101/MDM2regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control[J].Proc Natl Acad Sci U S A,98,1619-1624.
Li,M.,Brooks,C.L.,Kon,N.and Gu,W.(2004) A dynamic role of HAUSP in the p53-Mdm2 pathway[J].Mol Cell,13,879-886.
Li,M.,Brooks,C.L.,Wu-Baer,F.,Chen,D.,Baer,R.and Gu,W.(2003) Monoversus polyubiquitination:differential control of p53 fate by Mdm2[J].Science,302,1972-1975.
Li,M.,Chen,D.,Shiloh,A.,Luo,J.,Nikolaev,A.Y.,Qin,J.and Gu,W.(2002a)Deubiquitination of p53 by HAUSP is an important pathway for p53stabilization[J].Nature,416,648-653.
Li,M.,Luo,J.,Brooks,C.L.and Gu,W.(2002b) Acetylation of p53 inhibits its ubiquitination by Mdrn2.J Biol Chem,277,50607-50611.
Louria-Hayon,I.,Grossman,T.,Sionov,R.V.,Alsheich,O.,Pandolfi,P.P.and Haupt,Y.(2003) The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation[J].J Biol Chem,278,33134-33141.
Luo,J.,Su,F.,Chert,D.,Shiloh,A.and Gu,W.(2000) Deacetylation of p53modulates its effect on cell growth and apoptosis[J].Nature,408,377-381.
Marechal,V.,Elenbaas,B.,Piette,J.,Nicolas,J.C.and Levine,A.J.(1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes [J].Mol Cell Biol,14,7414-7420.
Marine,J.C.and Jochemsen,A.G.(2005) Mdmx as an essential regulator of p53activity[J].Biochem Biophys Res Commun,331,750-760.
Maya,R.,Balass,M.,Kim,S.T.,Shkedy,D.,Leal,J.F.,Shifman,O.,Moas,M.,Buschmann,T.,Ronai,Z.,Shiloh,Y.,Kastan,M.B.,Katzir,E.and Oren,M.(2001) ATM-dependent phosphorylation of Mdm2 on serine 395:role in p53activation by DNA damage[J].Genes Dev,15,1067-1077.
Mayo,L.D.and Donner,D.B.(2001) A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the.nucleus[J].Proc Natl Acad Sci U S A,98,11598-11603.
Meek,D.W.and Knippschild,U.(2003) Posttranslational modification of MDM2[J].Mol Cancer Res,1,1017-1026.
Michael,D.and Oren,M.(2003) The p53-Mdm2 module and the ubiquitin system [J].Semin Cancer Biol,13,49-58.
Moll,U.M.and Petrenko,O.(2003) The MDM2-p53 interaction[J].Mol Cancer Res,1,1001-1008.
Ogawara,Y.,Kishishita,S.,Obata,T.,Isazawa,Y.,Suzuki,T.,Tanaka,K.,Masuyama,N.and Gotoh,Y.(2002) Akt enhances Mdm2-mediated ubiquitination and degradation of p53[J].J Biol Chem,277,21843-21850.
Perry,M.E.,Piette,J.,Zawadzki,J.A.,Harvey,D.and Levine,A.J.(1993) The mdm-2 gene is induced in response to UV light in a p53-dependent manner [J].Proc Natl Acad Sci U S A,90,11623-11627.
Querido,E.,Blanchette,P.,Yan,Q.,Kamura,T.,Morrison,M.,Boivin,D.,Kaelin,W.G.,Conaway,R.C.,Conaway,J.W.and Branton,P.E.(2001) Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex[J].Genes Dev,15,3104-3117.
Rajendra,R.,Malegaonkar,D.,Pungaliya,P.,Marshall,H.,Rasheed,Z.,Brownell,J.,Liu,L.F.,Lutzker,S.,Saleem,A.and Rubin,E.H.(2004) Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53[J].J Biol Chem,279,36440-36444.
Roe,J.S.,Kim,H.,Lee,S.M.,Kim,S.T.,Cho,E.J.and Youn,H.D.(2006) p53stabilization and transactivation by avon Hippel-Lindau protein[J].Mol Cell,22,395-405.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Sharp,D.A.,Kratowicz,S.A.,Sank,M.J.and George,D.L.(1999) Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein[J].J Biol Chem,274,38189-38196.
Stad,R.,Little,N.A.,Xirodimas,D.P.,Frenk,R.,van der Eb,A.J.,Lane,D.P.,Saville,M.K.and Jochemsen,A.G.(2001) Mdmx stabilizes p53 and Mdm2via two distinct mechanisms[J].EMBO Rep,2,1029-1034.
Stad,R.,Ramos,Y.F.,Little,N.,Grivell,S.,Attema,J.,van Der Eb,A.J.and Jochemsen,A.G.(2000) Hdmx stabilizes Mdm2 and p53[J].JBiol Chem,275,28039-28044.
Stommel,J.M.and Wahl,G.M.(2004) Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation[J].Embo J,23,1547-1556.
Sui,G.,Affar el,B.,Shi,Y.,Brignone,C.,Wall,N.R.,Yin,P.,Donohoe,M.,Luke,M.P.,Calvo,D.and Grossman,S.R.(2004) Yin Yang 1 is a negative regulator of p53[J].Cell,117,859-872.
Tao,W.and Levine,A.J.(1999) P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2[J].Proc Natl Acad Sci U S A,96,6937-6941.
Tergaonkar,V.and Perkins,N.D.(2007) p53 and NF-kappaB crosstalk:IKKalpha tips the balance[J].Mol Cell,26,158-159.
Vogelstein,B.,Lane,D.and Levine,A.J.(2000) Surfing the p53 network[J].Nature,408,307-310.
Wang,C.and Chen,J.(2003) Phosphorylation and hspg0 binding mediate heat shock stabilization of p53[J].J Biol Chem,278,2066-2071.
Wang,C.,Ivanov,A.,Chen,L.,Fredericks,W.J.,Seto,E.,Rauscher,F.J.,3rd and Chen,J.(2005) MDM2 interaction with nuclear corepressor KAP1contributes to p53 inactivation[J].Embo J,24,3279-3290.
Wang,X.,Taplick,J.,Geva,N.and Oren,M.(2004) Inhibition of p53 degradation by Mdm2 acetylation[J].FEBS Lett,561,195-201.
Weber,J.D.,Taylor,L.J.,Roussel,M.F.,Sherr,C.J.and Bar-Sagi,D.(1999)Nucleolar Arf sequesters Mdm2 and activates p53[J].Nat Cell Biol,1,20-26.
Xirodimas,D.P.,Stephen,C.W.and Lane,D.P.(2001) Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm2-mediated degradation of p53[J].Exp Cell Res,270,66-77.
Yang,H.Y.,Wen,Y.Y.,Chen,C.H.,Lozano,G.and Lee,M.H.(2003) 14-3-3 sigma positively regulates p53 and suppresses tumor growth[J].Mol Cell Biol,23,7096-7107.
Yoon,S.Y.,Lee,Y.,Kim,J.H.,Chung,A.S.,Joo,J.H.,Kim,C.N.,Kim,N.S.,Choe,I.S.and Kim,J.W.(2005) Over-expression of human UREB1 in colorectal cancer:HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein[J].Biochem Biophys Res Commun,326,7-17.
Yu,Z.K.,Geyer,R.K.and Maki,C.G.(2000) MDM2-dependent ubiquitination of nuclear and cytoplasmic P53[J].Oncogene,19,5892-5897.
Zhang,Y.,Wolf,G.W.,Bhat,K.,Jin,A.,Allio,T.,Burkhart,W.A.and Xiong,Y.(2003) Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway[J].Mol Cell Biol,23,8902-8912.
Zhang,Y.and Xiong,Y.(2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF[J].Cell Growth Differ,12,175-186.
Zhao,Y.,Katzman,R.B.,Delmolino,L.M.,Bhat,I.,Zhang,Y.,Gurumurthy,C.B.,Germaniuk-Kurowska,A.,Reddi,H.V.,Solomon,A.,Zeng,M.S.,Kung,A.,Ma,H.,Gao,Q.,Dimri,G.,Stanculescu,A.,Miele,L.,Wu,L.,Griffin,J.D.,Wazer,D.E.,Band,H.and Band,V.(2007) The notch regulator MAML1interacts with p53 and functions asa coactivator[J].JBiol Chem,282,11969-11981.
Zhu,Q.,Yao,J.,Wani,G.,Wani,M.A.and Wani,A.A.(2001) Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53:evidence for the role of p300 in integrating ubiquitination and proteolysis[J].J Biol Chem,276,29695-29701.
Barr,E.and Tamms,G.(2007) Quadrivalent human papillomavirus vaccine[J].Clin lnfect Dis,45,609-607.
Behtash,N.and Mehrdad,N.(2006) Cervical cancer:screening and prevention[J].Asian Pac J Cancer Prev,7,683-686.
Brinkman,J.A.,Hughes,S.H.,Stone,P.,Caffrey,A.S.,Muderspach,L.I.,Roman,L.D.,Weber,J.S.and Kast,W.M.(2007) Therapeutic vaccination for HPV induced cervical cancers[J].Dis Markers,23,337-352.
Bryan,J.T.(2007) Developing an HPV vaccine to prevent cervical cancer and genital warts[J].Vaccine,25,3001-3006.
Butz,K.,Shahabeddin,L.,Geisen,C.,Spitkovsky,D.,Ullmann,A.and Hoppe-Seyler,F.(1995) Functional p53 protein in human papillomavirus-positive cancer cells[J].Oncogene,10,927-936.
Crook,T.,Wrede,D.,Tidy,J.A.,Mason,W.P.,Evans,D.J.and Vousden,K.H.(1992)Clonal p53 mutation in primary cervical cancer:association with human-papillomavirus-negative tumours[J].Lancet,339,1070-1073.
Crook,T.,Wrede,D.and Vousden,K.H.(1991) p53 point mutation in HPV negative human cervical carcinoma cell lines[J].Oncogene,6,873-875.
Cram,C.P.,Abbott,D.W.and Quade,B.J.(2003) Cervical cancer screening:from the Papanicolaou smear to the vaccine era[J].J Clin Oncol,21,224s-230s.
Doorbar,J.and Cubie,H.(2005) Molecular basis for advances in cervical screening [J].Mol Diagn,9,129-142.
Hietanen,S.,Lain,S.,Krausz,E.,Blattner,C.and Lane,D.P.(2000) Activation of p53 in cervical carcinoma cells by small molecules[J].Proc Natl Acad Sci U S A,97,8501-8506.
Ikenberg,H.,Matthay,K.,Schmitt,B.,Bauknecht,T.,Kiechle-Schwarz,M.,Goppinger,A.and Pfleiderer,A.(1995) p53 mutation and MDM2amplification are rare even in human papillomavirus-negative cervical carcinomas[J].Cancer,76,57-66.
Lin,Y.Y.,Alphs,H.,Hung,C.F.,Roden,R.B.and Wu,T.C.(2007) Vaccines against human papillomavirus[J].Front Biosci,12,246-264.
Manickam,A.,Sivanandham,M.and Tourkova,I.L.(2007) Immunological role of dendritic cells in cervical cancer[J].Adv Exp Med Biol,601,155-162.
Munoz,N.,Bosch,F.X.,Castellsague,X.,Diaz,M.,de Sanjose,S.,Hammouda,D.,Shah,K.V.and Meijer,C.J.(2004) Against which human papillomavirus types shall we vaccinate and screen? The international perspective[J].Int J Cancer,111,278-285.
Scheffner,M.,Huibregtse,J.M.,Vierstra,R.D.and Howley,P.M.(1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53[J].Cell,75,495-505.
Scheffner,M.,Munger,K.,Byme,J.C.and Howley,P.M.(1991) The state of the p53and retinoblastoma genes in human cervical carcinoma cell lines[J].Proc Natl Acad Sci USA,88,5523-5527.
Scheffner,M.and Whitaker,N.J.(2003) Human papillomavirus-induced carcinogenesis and the ubiquitin-proteasome system[J].Semin Cancer Biol,13,59-67.
Schmiedeskamp,M.R.and Kockler,D.R.(2006) Human papillomavirus vaccines[J].Ann Pharmacother,40,1344-1352.
Smith,J.S.,Lindsay,L.,Hoots,B.,Keys,J.,Franceschi,S.,Winer,R.and Clifford,G.M.(2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions:a meta-analysis update[J].Int J Cancer,121,621-632.
Tommasino,M.,Accardi,R.,Caldeira,S.,Dong,W.,Malanchi,I.,Smet,A.and Zehbe,I.(2003) The role of TP53 in Cervical carcinogenesis[J].Hum Murat,21,307-312.
Vousden,K.H.and Lu,X.(2002) Live or let die:the cell's response to p53[J].Nat Rev Cancer,2,594-604.
zur Hausen,H.(1996) Papillomavirus infections--a major cause of human cancers [J].Biochim Biophys Acta,1288,F55-78.