iASPP单克隆抗体的制备与应用及iASPP新的剪接体（iASPP-SV）抑制p21~（WAF1/CIP1）转录机制研究
摘要
第一部分抗人iASPP单克隆抗体的制备及研究应用
实验目的:应用脾脏内注射真核iASPP-SV表达质粒免疫的方法制备抗人iASPP单克隆抗体(McAb),并对其生物学特性进行初步研究。
实验方法:RT-PCR方法克隆iASPP-SV编码区cDNA。将扩增所得到的全长基因克隆到真核表达载体pcDNA3.1(+)中,并将iASPP-SV基因全长和基因片段克隆到原核表达载体pET28a中。诱导PIAF和PIAS载体在大肠杆菌Rosseta(DE3)中表达PIAF和PIAS蛋白。通过盐酸胍变性溶解包涵体,并经镍柱纯化得到重组PIAF和PIAS蛋白。
采用脾脏内注射真核pcDNA3.1-iASPP-SV(CIAF)免疫Balb/c小鼠3天后,取小鼠脾脏与小鼠骨髓瘤细胞(NS1)用传统的淋巴细胞杂交瘤技术制备抗人iASPP单克隆抗体。应用原核表达的iASPP-SV全长及iASPP-SV片段His-tag融合蛋白进行间接ELISA法筛选阳性克隆。并对亚克隆后的阳性杂交瘤细胞株所制备的抗体的生物学功能进行了初步鉴定。
实验结果:我们利用RT-PCR方法从人白血病细胞系U-937中克隆出癌基因iASPP-SV编码cDNA,成功构建iASPP-SV表达载体PIAF、PIAS和CIAF,重组质粒读码框和序列与预期一致。在IPTG诱导下,重组载体大肠杆菌Rosetta(DE3)菌株,表达产物经SDS-PAGE和western blot方法分析证实系PIAS和PIAF融合蛋白。利用Ni~(2+)鳌合层析的方法纯化PIAS和PIAF融合蛋白,经SDS-PAGE鉴定其纯度超过80%。用CIAF质粒通过脾脏内注射免疫所获得的小鼠脾脏细胞通过细胞融合、筛选和克隆化培养最后得到10株单克隆抗体细胞株。我们所获得的抗体能与天然iASPP-SV和iASPP蛋白及重组iASPP-SV蛋白特异性结合,而且实验表明所获得的抗体可以应用于western blot、免疫组织化学等实验。
实验结论:本研究成功地应用脾脏内注射真核iASPP-SV表达质粒免疫制备了针对人iASPP蛋白的抗体,该抗体能够特异识别iASPP-SV和iASPP两个异构体。为进一步对iASPP蛋白水平检测以及其功能、作用机制等实验研究奠定了良好的工作基础。
第二部分iASPP-SV能够与Sp1相互作用并抑制Sp1介导的p21WAF1/CIP1转录
研究目的:探讨iASPP-SV与转录因子Sp1相互作用和对Sp1介导的p21~(WAF1/CIP1)启动子转录的影响及其作用机制。
研究方法:将FLAG-iASPP-SV与Sp1质粒共转染293和KB细胞系应用免疫共沉淀、免疫荧光方法检测iASPP-SV能否与Sp1相结合及其在细胞核内共定位。应用荧光素酶报告基因和染色质免疫沉淀技术进一步深入研究iASPP-SV对Sp1介导的p21~(WAF1/CIP1)启动子的转录影响及其机制。
结果:我们将iASPP-SV与Sp1共转染细胞后发现iASPP-SV能够在细胞内与Sp1相结合,并共定位于细胞核内。iASPP-SV可以抑制含有Sp1 1-6结合位点的pGL3-Basic-p21~(WAF1/Cip1)-promoter以及仅含有Sp1 3-6结合位点的pGL3-Basic-p21~(WAF1/Cip1)-101-promoter荧光素酶报告质粒的转录活性。进一步研究发现iASPP-SV可以结合于p21~(WAF1/Cip1)启动子区的Sp1结合位点。
结论:iASPP-SV可以在细胞内结合Sp1并共定位于细胞核;iASPP-SV可以抑制Sp1介导的p21~(WAF1/Cip1)转录;iASPP-SV可以结合于p21~(WAF1/Cip1)启动子区的Sp1结合位点。
PartⅠPreparation of anti-human oncoprotein iASPP monoclonal antibody and its research application
Objective:To prepare the mouse anti-human iASPP monoclonal antibody by single-shoting plasmid DNA intrasplenic immunization and identify its biological characteristics.
Methods:The cDNA of human iASPP-SV was cloned by reverse transcriptase polymerase chain reaction(RT-PCR) from U937 cell line.The full-length cDNA of iASPP-SV was cloned into the eukaryotic expression vector pcDNA3.1(+) and the full-length cDNA or small fragment of iASPP-SV was cloned into the prokaryotic pET28a(+).The full-length or small fragment peptide of iASPP-SV with His-tag(PIAS and PIAF) was induced to express PIAS and PIAF proteins in E.coli Rosseta(DE3) strain by inclusion body, respectively.The PIAS and PIAF inclusion bodies were denatured by guanidine hydrochloride and were purified by by only one step of Ni~(2+) NTA chromatography.
After 3 days injecting the plasmid pcDNA3.1-iASPP(CIAF) into spleens of Balb/c mice once,the spleen cells were fused with NS1 cells.Then monoclonal antibodies were prepared by classical hybridoma technique.We used ELISA method to scan the fused clones by using the full length and small fragment of his-tag fusion iASPP-SV protein expressed by the prokaryotic cells.And we identified some biological functions of the antibodies produced by the positive subclones.
Results:We cloned the cDNA of iASPP-SV by RT-PCR from U937,and succeeded in constructing PIAF,PIAS and CIAF expression vector.The recombinant vector can express the small fragment and full length of iASPP-SV fusion proteins in E.coli Rosetta(DE3) strain induced by IPTG. The products were identified as by SDS-PAGE and Western blot.We purified the fusion protein by only one step of Ni~(2+) NTA chromatography,and the purity of the fusion protein was over 80%analyzed by SDS-PAGE.We prepared 10 hybridoma cell lines,which can secrete the antibodies against human iASPP proteins.And the antibodies can be applied in western blot、immunohistochemistry.
Conclusions:In tis study we prepared the mouse anti-human oncoprotein iASPP monoclonal antibodies by single-shoting plasmid pcDNA3.1-iASPP-SV DNA intrasplenic immunization successfully.The antibodies we prepared can identify the two isoform of iASPP:iASPP-SV and iASPP specifically. We founded the excellent base for the future works on examination of iASPP protein and its function and mechanism.
PartⅡiASPP-SV interacts with Sp1 and represses p21~(WAF1/CIP1) transcription mediated by Sp1
Objective:To investigate the interaction of iASPP-SV and transcriptional factor Sp1,the influence and mechanism of iASPP-SV on p21~(WAF1/CIP1) promotor mediated by Sp1.
Methods:We transfected the iASPP-SV and Sp1 into 293 and KB cells to find that whether iASPP-SV can interact in vivo and co-locate in nuclear. We further studied the the influence and mechanism of iASPP-SV on p21~(WAF1/CIP1) promotor mediated by Sp1 by using luciferase reporter and chromatin immunoprecipitation technologies.
Results:We found that iASPP-SV could interact with Sp1 in vivo and co-locate in nuclear,iASPP-SV can inhibit the transcriptional activities of pGL3-Basic-p21~(WAF1/Cip1)-promoter and p21~(WAF1/Cip1)-101-promoter luciferase reporter.And the further study showed iASPP-SV can bind Sp1 binding site on p21~(WAF1/Cip1) promoter.
Conclusions:iASPP-SV can interact with Sp1 in vivo and co-locate in nuclear;iASPP-SV can inhibit the transcriptional activities of p21~(WAF1/CIP1) promotor mediated by Sp1 and bind Sp1 binding site on p21~(WAF1/Cip1) promoter.
实验目的:应用脾脏内注射真核iASPP-SV表达质粒免疫的方法制备抗人iASPP单克隆抗体(McAb),并对其生物学特性进行初步研究。
实验方法:RT-PCR方法克隆iASPP-SV编码区cDNA。将扩增所得到的全长基因克隆到真核表达载体pcDNA3.1(+)中,并将iASPP-SV基因全长和基因片段克隆到原核表达载体pET28a中。诱导PIAF和PIAS载体在大肠杆菌Rosseta(DE3)中表达PIAF和PIAS蛋白。通过盐酸胍变性溶解包涵体,并经镍柱纯化得到重组PIAF和PIAS蛋白。
采用脾脏内注射真核pcDNA3.1-iASPP-SV(CIAF)免疫Balb/c小鼠3天后,取小鼠脾脏与小鼠骨髓瘤细胞(NS1)用传统的淋巴细胞杂交瘤技术制备抗人iASPP单克隆抗体。应用原核表达的iASPP-SV全长及iASPP-SV片段His-tag融合蛋白进行间接ELISA法筛选阳性克隆。并对亚克隆后的阳性杂交瘤细胞株所制备的抗体的生物学功能进行了初步鉴定。
实验结果:我们利用RT-PCR方法从人白血病细胞系U-937中克隆出癌基因iASPP-SV编码cDNA,成功构建iASPP-SV表达载体PIAF、PIAS和CIAF,重组质粒读码框和序列与预期一致。在IPTG诱导下,重组载体大肠杆菌Rosetta(DE3)菌株,表达产物经SDS-PAGE和western blot方法分析证实系PIAS和PIAF融合蛋白。利用Ni~(2+)鳌合层析的方法纯化PIAS和PIAF融合蛋白,经SDS-PAGE鉴定其纯度超过80%。用CIAF质粒通过脾脏内注射免疫所获得的小鼠脾脏细胞通过细胞融合、筛选和克隆化培养最后得到10株单克隆抗体细胞株。我们所获得的抗体能与天然iASPP-SV和iASPP蛋白及重组iASPP-SV蛋白特异性结合,而且实验表明所获得的抗体可以应用于western blot、免疫组织化学等实验。
实验结论:本研究成功地应用脾脏内注射真核iASPP-SV表达质粒免疫制备了针对人iASPP蛋白的抗体,该抗体能够特异识别iASPP-SV和iASPP两个异构体。为进一步对iASPP蛋白水平检测以及其功能、作用机制等实验研究奠定了良好的工作基础。
第二部分iASPP-SV能够与Sp1相互作用并抑制Sp1介导的p21WAF1/CIP1转录
研究目的:探讨iASPP-SV与转录因子Sp1相互作用和对Sp1介导的p21~(WAF1/CIP1)启动子转录的影响及其作用机制。
研究方法:将FLAG-iASPP-SV与Sp1质粒共转染293和KB细胞系应用免疫共沉淀、免疫荧光方法检测iASPP-SV能否与Sp1相结合及其在细胞核内共定位。应用荧光素酶报告基因和染色质免疫沉淀技术进一步深入研究iASPP-SV对Sp1介导的p21~(WAF1/CIP1)启动子的转录影响及其机制。
结果:我们将iASPP-SV与Sp1共转染细胞后发现iASPP-SV能够在细胞内与Sp1相结合,并共定位于细胞核内。iASPP-SV可以抑制含有Sp1 1-6结合位点的pGL3-Basic-p21~(WAF1/Cip1)-promoter以及仅含有Sp1 3-6结合位点的pGL3-Basic-p21~(WAF1/Cip1)-101-promoter荧光素酶报告质粒的转录活性。进一步研究发现iASPP-SV可以结合于p21~(WAF1/Cip1)启动子区的Sp1结合位点。
结论:iASPP-SV可以在细胞内结合Sp1并共定位于细胞核;iASPP-SV可以抑制Sp1介导的p21~(WAF1/Cip1)转录;iASPP-SV可以结合于p21~(WAF1/Cip1)启动子区的Sp1结合位点。
PartⅠPreparation of anti-human oncoprotein iASPP monoclonal antibody and its research application
Objective:To prepare the mouse anti-human iASPP monoclonal antibody by single-shoting plasmid DNA intrasplenic immunization and identify its biological characteristics.
Methods:The cDNA of human iASPP-SV was cloned by reverse transcriptase polymerase chain reaction(RT-PCR) from U937 cell line.The full-length cDNA of iASPP-SV was cloned into the eukaryotic expression vector pcDNA3.1(+) and the full-length cDNA or small fragment of iASPP-SV was cloned into the prokaryotic pET28a(+).The full-length or small fragment peptide of iASPP-SV with His-tag(PIAS and PIAF) was induced to express PIAS and PIAF proteins in E.coli Rosseta(DE3) strain by inclusion body, respectively.The PIAS and PIAF inclusion bodies were denatured by guanidine hydrochloride and were purified by by only one step of Ni~(2+) NTA chromatography.
After 3 days injecting the plasmid pcDNA3.1-iASPP(CIAF) into spleens of Balb/c mice once,the spleen cells were fused with NS1 cells.Then monoclonal antibodies were prepared by classical hybridoma technique.We used ELISA method to scan the fused clones by using the full length and small fragment of his-tag fusion iASPP-SV protein expressed by the prokaryotic cells.And we identified some biological functions of the antibodies produced by the positive subclones.
Results:We cloned the cDNA of iASPP-SV by RT-PCR from U937,and succeeded in constructing PIAF,PIAS and CIAF expression vector.The recombinant vector can express the small fragment and full length of iASPP-SV fusion proteins in E.coli Rosetta(DE3) strain induced by IPTG. The products were identified as by SDS-PAGE and Western blot.We purified the fusion protein by only one step of Ni~(2+) NTA chromatography,and the purity of the fusion protein was over 80%analyzed by SDS-PAGE.We prepared 10 hybridoma cell lines,which can secrete the antibodies against human iASPP proteins.And the antibodies can be applied in western blot、immunohistochemistry.
Conclusions:In tis study we prepared the mouse anti-human oncoprotein iASPP monoclonal antibodies by single-shoting plasmid pcDNA3.1-iASPP-SV DNA intrasplenic immunization successfully.The antibodies we prepared can identify the two isoform of iASPP:iASPP-SV and iASPP specifically. We founded the excellent base for the future works on examination of iASPP protein and its function and mechanism.
PartⅡiASPP-SV interacts with Sp1 and represses p21~(WAF1/CIP1) transcription mediated by Sp1
Objective:To investigate the interaction of iASPP-SV and transcriptional factor Sp1,the influence and mechanism of iASPP-SV on p21~(WAF1/CIP1) promotor mediated by Sp1.
Methods:We transfected the iASPP-SV and Sp1 into 293 and KB cells to find that whether iASPP-SV can interact in vivo and co-locate in nuclear. We further studied the the influence and mechanism of iASPP-SV on p21~(WAF1/CIP1) promotor mediated by Sp1 by using luciferase reporter and chromatin immunoprecipitation technologies.
Results:We found that iASPP-SV could interact with Sp1 in vivo and co-locate in nuclear,iASPP-SV can inhibit the transcriptional activities of pGL3-Basic-p21~(WAF1/Cip1)-promoter and p21~(WAF1/Cip1)-101-promoter luciferase reporter.And the further study showed iASPP-SV can bind Sp1 binding site on p21~(WAF1/Cip1) promoter.
Conclusions:iASPP-SV can interact with Sp1 in vivo and co-locate in nuclear;iASPP-SV can inhibit the transcriptional activities of p21~(WAF1/CIP1) promotor mediated by Sp1 and bind Sp1 binding site on p21~(WAF1/Cip1) promoter.
引文
1. Lu X. p53: a heavily dictated dictator of life and death. Curr Opin Genet Dev. 2005 Feb;15(1):27-33. Review.
2. Bergamaschi, D., Samuels, Y., O'Neil, N. J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33, 162-7.
3. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.Oncogene. 2004;23, 9007-16.
4. Yang, J. P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999:274,15662-70.
5. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53. J Mol Biol. 2007 May 11;368(4):1162-71.
6. Wolff J. A ,Malone R. W .Williams P , et al. Direct gene transfer into mouse muscle in vivo . Science , 1990 ,247 :1465 -1468.
7. Tang DC, Devit M, Johnston SA. Genetic immunization is a simple method for elicting an immune response. Nature. 1992, 356:152-154,
8. Spier RE. Nucleic acid vaccines. 17-18 May 1994, WHO (OMS), Geneva,Switzerland. Vaccine. 1995 Jan;13(1):131-2.
9. Spitz M, Spitz L, Thorpe R, Eugui E. Intrasplenic primary immunization for the production of monoclonal antibodies. J Immunol Methods. 1984 May 11;70(1) :39-43.
10. Velikovsky CA, Cassataro J, Sanchez M, et al. Single-shot plasmid DNA intrasplenic immunization for the production of monoclonal antibodies. Persistent expression of DNA. J Immunol Methods. 2000 Oct 20;244(1-2): 1-7.
11. Moonsom S, Khunkeawla P, Kasinrerk W. Production of polyclonal and monoclonal antibodies against CD54 molecules by intrasplenic immunization of plasmid DNA encoding CD54 protein. Immunol Lett. 2001 Feb 1;76(1):25-30.
12. Kasinrerk W, Moonsom S, Chawansuntati K. Production of antibodies by single DNA immunization: comparison of various immunization routes.Hybrid Hybridomics. 2002 Aug;21(4):287-93.
13. Jiao S, Williams P, Berg RK, et al. Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther 1992;3:21 -33.
14. Davis HL, Whalen RG, and Demeneix BA. Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum Gene Ther 1993;4:151 - 159.
15. Major ME, Vitvitski L, Mink MA, et al. DNA-based immunization with chimeric vectors for the induction of immune responses against the hepatitis C virus nucleocapsid. J Virol 1995;69:5798 - 5805.
16. Bohm W, Kuhrober A, Paier T, et al. DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection. J Immunol Methods 1996;193:29-40.
17. Gray D, and Skarvall H: B cell memory is short-lived in the absence of antigen. Nature 1988;336:70-73.
18. Wang B, Boyer J, Srikantan V, et al. DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates. DNA Cell Biol 1993;12:799-805.
19. Takashima A, and Morita A. Dendrictic cells in genetic immunization.J Leukoc Biol 1999;66:350-356.
20. Qian M, Chen S, Li X, et al. Cloning and expression of human UDP-glucuronosyltransferase 1A4 in Bac-to-Bac system. Biochem. Biophys.Res. Commun, 2004,319(2): 386-92.
21. OuelletteT, Destrau S, OuelletteT, et al. Production and purification of refolded recombinant human IL-7 from inclusion bodies. Protein Expr Purif. 2003 Aug;30(2): 156-66.
22. Richter W, Hermsdorf T, Kronbach T, et al. Refolding and purification of recombinant human PDE7A expressed in Escherichia coli as inclusion bodies. Protein Expr Purif. 2002 Jun;25(1):138-48.
23. Margetts MB, Barr IG, Webb EA. Overexpression, purification, and refolding of a Porphyromonas gingivalis cysteine protease from Escherichia coli. Protein Expr Purif. 2000 Apr;18(3):262-8.
24. Stoscheck, CM. Quantitation of Protein. Methods in Enzymology.1990;182: 50-69.
25. Zhang, X., Wang, M., Zhou, C., et al. The expression of iASPP in acute leukemias. Leuk Res. 2005:29,179-83.
1.Sullivan A, Lu X. ASPP: a new family of oncogenes and tumour suppressor genes. Br J Cancer. 2007 Jan 29;96(2):196-200. Epub 2007 Jan 9. Review.
2. Liu ZJ, Lu X, Zhong S. ASPP—Apoptotic specific regulator of p53. Biochim Biophys Acta. 2005 Sep 25;1756(1):77-80. Review.
3. Samuels-Lev Y, O'Connor DJ, Bergamaschi D, et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001; 8:781-794.
4. Gorina, S. & Pavletich N. P. (1996). Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science.274, 1001-5.
5. Bergamaschi, D., Samuels, Y., Jin, B., et al. ASPP1 and ASPP2: common activators of p53 family members. 2004;Mol Cell Biol. 24,1341-50.
6. Yang, J.P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999;274,15662-70.
7. Bergamaschi, D., Samuels, Y., O'Neil, N.J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33,162-7.
8. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.Oncogene. 2004;23, 9007-16.
9. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53.J Mol Biol.2007 May 11;368(4):1162-71.
10.李圣爱。p21WAF1/CIP1基因上游主要转录调控序列区及其相关功能。医学分子生物学杂.2001;23(2):70-74.
11.Koutsodontis G,Tentes I,Papakosta P,et al.Spl plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cipl) gene by the p53 tumor suppressor protein.J Biol Chem.2001 Aug 3;276(31):29116-25.Epub 2001 May 30.
12.Takada N,Sanda T,Okamoto H,et al.RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Spl actions.J Virol.2002 Aug;76(16):8019-30.
13.Kathryn E.Boyd and Peggy J.Farnham.Coexamination of Site-Specific Transcription Factor Binding and Promoter Activity in Living Cells.Mol.Cell.Biol.1999;19:8393-8399.
14.Shang Y,Hu X,DiRenzo J,et al.Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.Cell.2000 Dec 8;103(6):843-52.
15.Yin D,Ong JM,Hu J,et al.Suberoylanilide hydroxamic acid,a histone deacetylase inhibitor:effects on gene expression and growth of glioma cells in vitro and in vivo.Clin Cancer Res.2007 Feb 1;13(3):1045-52
16.Myzak MC,Karplus PA,Chung FL,et al.A novel mechanism of chemoprotection by sulforaphane:inhibition of histone deacetylase.Cancer Res.2004 Aug 15;64(16):5767-74.
17.Kondo Y,Issa JP.Enrichment for histone H3 lysine 9 methylation at Alu repeats in human ceils.J Biol Chem.2003 Jul 25;278(30):27658-62. Epub 2003 Apr 30.
18. Milutinovic S, Brown SE, Zhuang Q, et al. DNA methyltransferase 1 knock down induces gene expression by a mechanism independent of DNA methylation and histone deacetylation. J Biol Chem. 2004 Jul 2;279(27):27915-27. Epub 2004 Apr 15.
19. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al.Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004 Feb 13;303(5660):1010-4.
20. Yin Y, Tainsky MA, Bischoff FZ, et al. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992 Sep 18;70(6):937-48.
21. Kastan MB, Zhan Q, el-Deiry WS, et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71 (4):587-97. )
22. Harper JW, Adami GR, Wei N, et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of Gl cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805-16.
23. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701-4.
24. Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16; 366 (6456) :707-10.
25. Dulic V, Kaufmann WK, Wilson SJ, et al. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced Gl arrest. Cell. 1994 Mar 25;76(6):1013-23.
26. Zhang H, Xiong Y, Beach D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell.1993 Sep;4(9):897-906.
27. Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16; 366 (6456): 707-10.
28. Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor beta responsive elements in the WAFl/Cip1/p21 promoter. J Biol Chem.1995 Dec 1;270(48):28623-8
29. Yamagishi H, Oka T, Nomura H, et al. Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.J Biol Chem. 1997 Aug 29;272(35):22199-206.
30. Sowa Y, Orita T, Minamikawa S, et al .Histone deacetylase inhibitor activates the WAFl/Cipl gene promoter through the Spl sites. Biochem Biophys Res Commun. 1997 Dec 8;241 (1):142-50.
31. Lee SJ, Ha MJ, Lee J, et al. Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAFl/CIPl) in human prostate carcinoma cells. J Biol Chem. 1998 Apr 24;273(17):10618-23.
32. Prowse DM, Bolgan L, Molndr A, et al. Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in keratinocyte differentiation. J Biol Chem. 1997 Jan 10;272(2):1308-14.
33. Biggs JR, Kudlow JE, Kraft AS. The role of the transcription factor Spl in regulating the expression of the WAFl/CIPl gene in U937 leukemic cells. J Biol Chem. 1996 Jan 12;271(2):901-6.
34. Somasundaram K, Zhang H, Zeng YX, et al. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAFl/CiP1.Nature. 1997 Sep 11;389(6647):187-90.
35. Somasundaram K, Zhang H, Zeng YX, et al. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAFl/CiP1.Nature. 1997 Sep 11;389(6647):187-90.
36. Kardassis D, Papakosta P, Pardali K, et al. c-Jun transactivates the promoter of the human p21WAFl/Cipl gene by acting as a superactivator of the ubiquitous transcription factor Spl. J Biol Chem 1999, 274,29572 - 29581.
37. Shao Z., Robbin s P.D. Differential regulation of E2F and Spl-mediated transcription by G1 cyclins. Oncogene. 1995; (19):221-228.
38. Shao Z, Ruppert S, Robbins P. D et al. The retinoblastoma susceptibility gene product binds directly to the human TATA-binding protein-associated factor TAFII250, Proc. Natl. Acad. Sci. USA 92 (1995)3115-3119.
39. Adnane J, Shao Z, P. D. Robbins, et al. Cyclin D1 associates with the TBP-associated factor TAFII250 to regulate Spl-mediated transcription,Oncogene 18 (1999) 239-247
40. Gartel AL, Ye X, Goufman E, et al. Myc represses the p21 (WAFl/CIP1) promoter and interacts with Spl/Sp3. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4510-5. Epub 2001 Mar 27.
41. Mantovani F, Tocco F, Girardini J, et al. The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nat Struct Mol Biol. 2007 Oct;14(10):912-20. Epub 2007 Sep 30.
42. Bergamaschi D, Samuels Y, Sullivan A, et al. iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nat Genet. 2006 Oct;38(10): 1133-41. Epub 2006 Sep 10.
43. Trigiante G, Lu X. ASPP [corrected] and cancer. Nat Rev Cancer. 2006 Mar;6(3):217-26. Review. Erratum in: Nat Rev Cancer. 2006 May;6(5):414.
44. Naumovski L, Cleary ML. The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell cycle progression at G2/M. Mol Cell Biol 1996;16: 3884-3892.
45. Ao Y, Rohde LH, Naumovski L. p53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis. Oncogene. 2001 May 10;20(21):2720-5.
46. Tidow H, Veprintsev DB, Freund SM, et al. Effects of oncogenic mutations and DNA response elements on the binding of p53 to p53-binding protein 2 (53BP2). J Biol Chem. 2006 Oct 27;281(43):32526-33. Epub 2006 Aug 2.
47. Yang JP, Hori M, Takahashi N, et al. NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene. 1999; 18:5177-5186.
48. Helps NR, Barker HM, Elledge SJ, et al. Protein phosphatase 1 interacts with p53BP2, a protein which binds to the tumour suppressor p53. FEBS Lett 1995; 377: 295-300.
49. Espanel X, Sudol M. Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. J Biol Chem. 2001;276:14514-14523.
50. Nakagawa H, Koyama K, Murata Y, et al. APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor,binds to p53-binding protein2 and translocates it to the perinucleus.Cancer Res. 2000; 60: 101-105.
51. Cao Y, Hamada T, Matsui T, et al. Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. Biochem Biophys Res Commun. 2004; 315: 788-795.
52. Bell HS, Dufes C, O'Prey J, et al. A p53-derived apoptotic peptide derepresses p73 to cause tumor regression in vivo. J Clin Invest. 2007 Apr;117(4):1008-18. Epub 2007 Mar 8.
53. Aoyama N, Nagase T, Sawazaki T, et al. Overlap of the p53-responsive element and cAMP-responsive element in the enhancer of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1992 Jun 15; 89 (12) : 5403-7.
1. Linzer DI, Levine AJ. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43-52.
2. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261-3..
3. Jenkins JR, Rudge K, Currie GA. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13-19;312(5995):651-4.
4. Mowat M, Cheng A, Kimura N, et al. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985 Apr 18-24;314(6012):633-6.
5. Chen PL, Chen YM, Bookstein R, et al. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576-80.
6. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature.1992 Mar 19;356(6366):215-21.
7. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233-8.
8. Caron de Fromentel C, Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1—15. Review.
9. Bert Vogelstein, David Lane and Arnold J. Levine. Surfing the p53 network. Nature, 2000,408:307-310.
10. Wolf, D., Harris, N., Goldfinger, N., and Rotter, V. 1985. Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. Mol. Cell. Biol. 5: 127-132.
11. Flaman, J.-M., Waridel, F., Estreicher, A., et al. The human tumor suppressor gene p53 is alternatively spliced in normal cells. 1996.Oncogene 12: 813-818.
12. Courtois, S., Verhaegh, G., North, S., et al. N-p53, a natural isoform of p53 lacking the first transactivation omain, counteracts growth suppression by wild-type p53. Oncogene. 2002;21: 6722-6728.
13. Yin, Y., Stephen, C. W., Luciani, M. G., et al. p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. 2002. Nat. Cell Biol. 4: 462-467.
14. Ghosh, A., Stewart, D., and Matlashewski, G. Regulation of human p53 activity and cell localization by alternative splicing. 2004. Mol. Cell.Biol. 24: 7987-7997
15. Bourdon JC, Fernandes K, Murray-Zmijewski F, et al.p53 isoforms can regulate p53 transcriptional activity. 2005. Genes Dev 19: 2122-2137.
16. Hussain SP, Harris CC. p53 mutation spectrum and load: the generation of hypotheses linking the exposure of endogenous or exogenous carcinogens to human cancer. Mutat Res. 1999 Jul 16;428 (1-2):23-32. Review.
17. El-Deiry, W. S., Kern, S.E., et al. Definition of a consensus binding site for p53. Nat Genet. 1992;1:45-9.
18. Funk, W. D., Pak, D. T., Karas, R. H., et al. A transcriptionally active DNA-binding site for human p53 protein complexes. Mol Cell Biol.1992;12:2866-71.
19. Foster BA, Coffey HA, MorinMJ, et al. Pharmacological rescue of mutant p53 conformation and function. Science. 1999 Dec 24;286(5449):2507-10.
20. Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer. 2004 Oct;4(10):793-805. Review.
21. Moll UM, Erster S, Zaika A. p53, p63 and p73—solos, alliances and feuds among family members. Biochim Biophys Acta. 2001 Dec 28;1552(2):47-59. Review.
22. Kaghad M, Bonnet H, Yang A, et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809-19.
23. Flores ER, Tsai KY, Crowley D, et al. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature. 2002 Apr 4;416(6880): 560-4.
24. Okada Y, Osada M, Kurata S, et al. p53 gene family p51 (p63)-encoded,secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation. Exp Cell Res. 2002 Jun 10;276(2):194-200.
25. Senoo M, Tsuchiya I, MatsumuraY, et al. Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human squamous cell carcinomas:expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51. Br J Cancer. 2001 May 4;84(9):1235-41.
26. Dumaz N, Milhe DM, Meek DW. Protein Kinase CK1 is a p53 threonine-18 Kinase which requires prior phosphorylation of serine 15. FEBS Lett ,1999 ,463 :312-316.
27. Hirao A, Kong YY, Matsuoka S, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000 Mar 10;287(5459):1824-7.
28. Banin S, Moyal L, Shieh S, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998 Sep 11;281(5383):1674-7.
29. Canman CE, Lim DS, Cimprich KA, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 1998 Sep 11;281(5383): 1677-9.
27. Momand, J., Zambetti, G. P., Olson, D. C., George, D., and Levine,A. J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69: 1237-1245, 1992.
28. Wu, L. and Levine, A. J. Differential regulation of the p21/WAF-1 and MDM2 genes after high-dose UV irradiation: p53-dependent and p53-independent regulation of the MDM2 gene. 1997, Mol. Med., 3: 441 -451.
29. Barak, Y., Juven, T., Haffner, R., and Oren, M. The MDM2 expression is induced by wild type p53 activity. 1993, EMBO J., 12: 461-468.
30. Chen, J., Marechal, V., and Levine, A. J. Mapping of the p53 and mdm-2 interaction domains. 1993, Mol. Cell. Biol., 13: 4107-4114.
31. Picksley, S. M. and Lane, D. P. The p53-MDM2 autoregulatory feedback loop: a paradigm for the regulation of growth control by p53? BioEssays.1993; 15: 689-690.
32. Haupt, Y., Maya, R., Kazaz, A., et al. MDM2 promotes the rapid degradation of p53. Nature, 1997;387: 296-299.
33. Kubbutat, M. H., Jones, S. N., and Vousden, K. H. Regulation of p53 stability by MDM2. Nature. 1997;387: 299-303.
34. Bottger, A., Bottger, V., Sparks, A., Liu, W. L., Howard, S. F., and Lane, D. P. Design of a synthetic MDM2-binding mini protein that activates the p53 response in vivo. Curr. Biol. 1997;7:860 - 869.
35. Maki, C. G. Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2. J. Biol. Chem. 1999; 274: 16531-16535.
36. Shirangi, T. R., Zaika, A., and Moll U. M. Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage.2002. FASEB J., 16: 420-422.
37. Lavin MF, Gueven N. The complexity of p53 stabilization and activation.Cell Death Differ. 2006 Jun;13(6):941-50. Review.
38. Lev Bar-Or R, Maya R, Segel LA, et al. Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11250-5.
39. Buschmann T, Fuchs SY, Lee CG, et al. SIMM modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell. 2000 Jun 23;101(7):753-62.
40. Zhang Y, Xiong Y. Control of p53 ubiquitirmtion and nuclear export bv MDM2 and ARF. Cell Growth Difer, 2001, 12(4): 175-186.
41. Tolbert D, Lu X, Yin C, et al. p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo. Mol Cell Biol. 2002 Jan;22(1):370-7.
42. Xirodimas D, Saville MK, Edling C, et al. Different effects of pHARF on the levels of ubiquitinated p53 and Mdm2 in vivo. Oncogene. 2001 Aug 16; 20 (36): 4972-83.
43. Ho GH, Calvano JE, Bisogna M, et al. Genetic alterations of the pl4ARF-hdm2-p53 regulatory pathway in breast carcinoma. Breast Cancer Res Treat.2001 Feb;65(3):225-32.
44. Su JD, MAYO LD, DONNER DB, et al. PTEN and phosphatidylinositol 3'-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment. Cancer Res, 2003, 63(13):3585-3592.
45. OGAWARA Y, KISHISHITA S, OBATA T, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem, 2002, 277(24): 21843-21850.
46. YAN X, FRASERM, QIU Q, et al. Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a P53-dependent manner. Gynecol Oncol , 2006,102 (2):348-355.
47. CHANG CJ, FREEMAN DJ, WU H. PTEN regulates Mdm2 expression through the P1 promoter. J Biol Chem, 2004, 279(28):29841-29848.
48. FREEMAN DJ, LI AG, WEI G, et al. PTEN tumor suppressor regulates P53 protein levels and activity through phosphatase-dependent and-independent mechanisms [J]. Cancer Cell, 2003, 3(2):117-130.
49. OKUMURA K, ZHAO M, DEPINHO RA, et al. PTEN: a novel anti-oncogenic function independent of phosphatase activity. Cell Cycle, 2005,4(4):540-542.
50. PAEZ J, SELLERS WR. PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res, 2003, 115:145-167.
51. KOMAZAWA N, SUZUKI A , SANO S, et al. Tumorigenesis facilitated by Pten deficiency in the skin : Evidence of P53-Pten complex formation on the initiation phase. Cancer Sci,2004, 95(8) :639 - 643.
52. TANG Y, ENG C. PTEN autoregulates its expression by stabilization of p53 in a phosphatase-independent manner. Cancer Res, 2006,66:736-742.
53. STAMBOLIC V, MACPHERSON D, SAS D, et al. Regulation of PTEN transcription by P53. Mol Cell, 2001, 8(2):317-325.
54. WANG J, OUYANG W, LI J, et al. Loss of tumor suppressor p53 decreases PTEN expression and enhances signaling pathways leading to activation of activator protein 1 and nuclear factor kappaB induced by UV radiation.Cancer Res, 2005, 65(15):6601 -6611.
55. Garkavtsev I, Grigorian IA, Ossovskaya VS, et al. The candidate tumour suppressor p33INGl cooperates with p53 in cell growth control. Nature.1998 Jan 15;391(6664):295-8.
56. Zhang Y, Xiong Y. A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science. 2001 Jun 8;292(5523):1910-5.
57. Shaw, P., Freeman, J., Bovey, R. & Iggo, R. Regulation of specific DNA binding by p53: evidence for a role for O-glycosylation and charged residues at the carboxy-terminus. Oncogene. 1996; 12, 921-930.
58. Wesierska-Gadek, J., Bugajska-Schretter, A. & Cerni, C.ADP-ribosylation of p53 tumor suppressor protein: mutant but not wild-type p53 is modified. J. Cell Biochem. 1996; 62:90-101.
59. Gatti, A., Li, H. H., Traugh, J. A. et al. Phosphorylation of human p53 on Thr-55. Biochemistry. 2000;39, 9837-9842.
60. Waterman, M. J., Stavridi, E. S., Waterman, J. L. et al. ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nature Genet. 1998; 19, 175-178.
61. Colman MS , Afshari CA , Barrett JC. Regulation of p53 stability and activity in response to genotoxic stess. Mutat Res , 2000 ; 462 :179-188.
62. Oda K, Arakanca H , Tanaka T , et al. p53AIPl ,a potential mediator of p53 dependent apoptosis , and its regulation by ser-462 phosphorylated p53. Cell , 2000; 102 :8492862.
63. Haneda, M. et al. Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA-damaging stressinduced phospho-serine 15 of p53.FEBS Lett. 2004; 567, 171 - 174.
64. Fan, G., Ma, X., Wong, P. Y., et al. p53 dephosphorylation and p21 (Cipl/Wafl) translocation correlate with caspase-3 activation in TGF-β1-induced apoptosis of HuH-7 cells. Apoptosis. 2004; 9, 211-221.
65. Pluquet O , Hainaut P. Genotoxic and non-genotoxic pathways of p53 induction. Cancer Lett , 2001 ,174 :1-15.
66. Hofmann TG, Möller A , Sirma H , et al . Regulation of p53 activity by its interaction with homeodomain 2 interacting protein kinase-2. Nat Cell Biol. 2002 ,4 : 1-10.
67. Brooks CL, Gu W. p53 ubiquitination: Mdm2 and beyond. Mol Cell. 2006 Feb 3;21(3):307-15. Review.
68. Rodriguez, M. S. et al. SUMO-1 modification activates the transcriptional response of p53. EMBO J. 1999; 18, 6455-6461.
69. Gostissa, M. et al. Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J. 1999; 18, 6462-6471.
70. Melchior, F. & Hengst, L SUMO-1 and p53. Cell Cycle 2002; 1, 245 - 249.
71. Chen, L. & Chen, J. MDM2-ARF complex regulates p53 sumoylation.Oncogene 2003; 22, 5348-5357.
72. Braithwaite AW, Del Sal G, Lu X. Some p53-binding proteins that can function as arbiters of life and death. Cell Death Differ. 2006 Jun;13(6):984-93.
73. Prives C and Hall PA. The p53 pathway. J. Path. 1999; 187: 112-126.
74. Zilfou J, Hoffman WH, Sank M, et al. The corepressor mSin3a interacts with the proline-rich domain of p53 and protects p53 from proteasome mediated degradation. Mol. Cell. Biochem. 2001,21: 3974-3985.
75. Iwabuchi, K., Bartel, P. L., Li, B., et al. Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci U S A.1994;91,6098-102.
76. Gorina, S. & Pavletich N. P. (1996). Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science.274,1001-5.
77. Naumovski, L. & Cleary, M. L. The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell cycle progression at G2/M. Mol Cell Biol. 1996;16,3884-92.
78. Takahashi N, Kobayashi S, Jiang X, et al. Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative splicing. Biochem Biophys Res Commun. 2004 Mar 5;315(2):434-8.
79. Ao Y, Rohde LH, Naumovski L. p53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis. Oncogene. 2001 May 10;20(21):2720~5.
80. Kobayashi S, Kajino S, Takahashi N, et al. 53BP2 induces apoptosis through the mitochondrial death pathway. Genes Cells. 2005 Mar;10(3): 253-60.
81. Cao Y, Hamada T, Matsui T, et al. Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. Biochem Biophys Res Commun. 2004 Mar 19;315(4):788-95.
82. Yang JP, Hori M, Takahashi N, et al. NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene. 1999 Sep 16;18(37):5177-86.
83. Lopez CD, Ao Y, Rohde LH, et al. Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53. Mol Cell Biol.2000 Nov;20(21):8018-25.
84. Nakagawa H, Koyama K, Murata Y, et al. APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor,binds to p53-binding protein 2 and translocates it to the perinucleus.Cancer Res. 2000 Jan 1;60(1):101-5.
85. Samuels-Lev, Y., O'Connor, D. J., Bergamaschi, D., et al. ASPP proteins specifically stimulate the apoptotic function of p53. 2001; Mol Cell. 8, 781-94.
86. Bergamaschi, D., Samuels, Y., Jin, B., et al. ASPP1 and ASPP2: common activators of p53 family members. 2004;Mol Cell Biol. 24,1341-50.
87. Iwabuchi K, Li B, Massa HF, et al. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. J Biol Chem. 1998 Oct 2;273(40):26061-8.
88. Bergamaschi D, Samuels Y, Zhong S, et al. Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation.Oncogene. 2005 May 26;24(23):3836-41.
89. Fogal V, Kartasheva NN, Trigiante G, et al. ASPP1 and ASPP2 are new transcriptional targets of E2F. Cell Death Differ. 2005 Apr; 12(4):369-76.
90. Liu ZJ, Lu X, Zhang Y, et al. Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53. FEBS Lett. 2005 Mar 14;579(7):1587-90.
91. Yang, J. P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999;274,15662-70.
92. Bergamaschi, D., Samuels, Y., O'Neil, N. J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33, 162-7.
93. Liu ZJ, Zhang Y, Zhang XB, et al. Abnormal mRNA expression of ASPP members in leukemia cell lines. Leukemia. 2004 Apr;18(4):880.
94. Zhang, X., Wang, M., Zhou, C., et al.The expression of iASPP in acute leukemias. Leuk Res. 2005;29, 179-83.
95. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization. Oncogene. 2004;23, 9007-16.
96. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53. J Mol Biol. 2007 May 11; 368(4):1162-71.
97. Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr. Biol. 2007; 17, 1298-1307.
98. Chang TC, Wentzel EA, Kent OA. et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 2007; 26, 745-752.
99. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447, 1130-1134.
100. Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell.2007;26,731-743.
101. Tarasov V, Jung P, Verdoodt B,et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. 2007;Cell Cycle 6,1586 - 1593.
102. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116, 281-297.
103. Zamore, P. D. & Haley, B. Ribo-gnome: the big world of small RNAs.Science 2005;309, 1519- 1524.
104. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene.2007 Jul 26;26(34):5017-22.
105. Zhao R, Gish K, Murphy M, et al. Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 2000 Apr 15;14(8):981-93.
106. Wei, C. L., Wu, Q., Vega, V. B., et al. A GlobalMap of p53 Transcription-Factor Binding Sites in the Human Genome. Cell.2006;124:207-19
107. Fisher DE. The p53 tumor suppressor: critical regulator of life & death in cancer. Apoptosis, 2001, 6(1-2): 7—15.
108. Cory, S. and Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647-656.
109. Nakano K, Vousden KH. PUMA ,a novel proapoptotic gene is induced by p53. Molecular Cell, 2001, 7(3):683-694.
110. Yu J, Zhang L, Hwang PM, et al. PUMA induces the rapid apoptosis of colorectal cancer cell. Molecular Cell, 2001, 7(3):673-682.
111. Han JW, Flemington C, Houghton AB, et al. Expression of bbc3, a pro-apoptotic BH-3only gene,is regulated by diverse cell death and survival signals. Proc Natl Acad Sci U S A, 2001, 98(20): 11318-11323..
112. Oda, E., Ohki, R., Murasawa, H., et al. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.Science 288, 1053-1058.
113. Oda K, Arakawa H, Tanaka T, et al. p53AIPl, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.Cell. 2000 Sep 15;102(6):849-62.
114. Boldin MP, Mett IL, Varfolomeev EE, et al. Self-association of the "death domains" of the p55 tumor necrosis factor (TNF) receptor and Fas/APOl prompts signaling for TNF and Fas/APOl effects. J Biol Chem. 1995 Jan 6; 270(1): 387-91.
115. Shimasaki S, Koba A, Mercado M, et al. Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA. Biochem Biophys Res Commun. 1989 Dec 15;165(2):907-12.
116. Nagata, S. and Golstein, P. (1995). The Fas death factor. Science 267, 1449-1456.
117. Muller, M., Wilder, S., Bannasch, D., Israeli, D., Lehlbach, K.,Li-Weber, M., Friedman, S. L., Galle, P. R., Stremmel, W., Oren, M. et al. (1998). p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J. Exp. Med. 188, 2033-2045.
118. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004 Feb 13;303(5660):1010-4.
119. Wahl GM, Linke SP, Paulson TG, et al. Maintaining genetic stability through TP53 mediated checkpoint control. Cancer Surv. 1997; 29:183 - 219.
120. Cheung KJ Jr, Mitchell D, Lin P, et al.The tumor suppressor candidate p33(INGl) mediates repair of UV-damaged DNA. Cancer Res. 2001 Jul 1;61(13):4974-7.
121. Kaina B. DNA damage—triggered apoptosis: critical role of DNA repair, double strand breaks, cell proliferation and signaling. Biochem Pharmacol, 2003, 66(8): 1547-1554)c
122. Schwarte-Waldhoff I, Volpert 0V, Bouck NP, et al. Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9624-9.
123. Yu JL, Rak JW , Comber BL, et al. Efect of p53 status on tumor response to antiangiogenic therapy. Science, 2002; 295: 1526-1528.
124. Aranda-Anzaldo A, Dent MA. Developmental noise, ageing and cancer. Mech Ageing Dev. 2003 Jun;124(6):711-20. Review.
125. Xu L, Pirollo KF,Tang WH, et al. Transferrin-liposome mediate systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum Gene Ther, 1999; 10: 2941-2952.
126. Foster BA, Cofey HA, Morin MJ, et al. Pharmacological rescue of mutant p53 conformation and funetion. Science. 1999, 286(549):2507-2510
127. Bullock AN, Fersht AR. Rescuing the function of mutant p53. Nat Rev Cancer. 2001, 1(1): 68—76.) .
128. Bottger A, Bottger V, Sparks A, et al. Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo. Curr Biol, 1997;7(11): 860-869.
129. O'Keefe K, Li H, Zhang Y.Nucleocytoplasmic shuttling of p53 is essential for MDM2-mediated cytoplasmic degradation but not ubiquitination.Mol Cell Biol. 2003 Sep;23(18):6396-405.
130. Almog N, Rotter V. An insight into the life of p53: a protein coping with many functions! Review of the 9th p53 Workshop, Crete, May 9-13, 1998.Biochim Biophys Acta. 1998 Nov 26;1378(3):R43-54.
131. Chang EH, Pirollo KF, Bouker KB, et al. Tp53 gene therapy: a key to modulating resistance to anticancer therapies? Mol Med Today,2000, 6(9): 358-364.
132. Swisher SG, Roth JA. Clinical update of Ad-p53 gene therapy for lung cancer. Surg Oncol Clin N Am, 2002, 11(3):521-535.
133. Braithwait A. W and Prives C. L. p53: more research and more questions.Cell Death and Differentiation (2006) 13, 877-880.
134. Bourdon J. C, Laurenzi V. De, Melino G et al. p53: 25 years of research and more questions to answer. Cell Death and Differentiation (2003) 10,397 - 399.
135. Jegga AG, Inga A, Menendez D, Aronow BJ, Resnick MA. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):944-9. Epub 2008 Jan 10.
2. Bergamaschi, D., Samuels, Y., O'Neil, N. J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33, 162-7.
3. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.Oncogene. 2004;23, 9007-16.
4. Yang, J. P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999:274,15662-70.
5. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53. J Mol Biol. 2007 May 11;368(4):1162-71.
6. Wolff J. A ,Malone R. W .Williams P , et al. Direct gene transfer into mouse muscle in vivo . Science , 1990 ,247 :1465 -1468.
7. Tang DC, Devit M, Johnston SA. Genetic immunization is a simple method for elicting an immune response. Nature. 1992, 356:152-154,
8. Spier RE. Nucleic acid vaccines. 17-18 May 1994, WHO (OMS), Geneva,Switzerland. Vaccine. 1995 Jan;13(1):131-2.
9. Spitz M, Spitz L, Thorpe R, Eugui E. Intrasplenic primary immunization for the production of monoclonal antibodies. J Immunol Methods. 1984 May 11;70(1) :39-43.
10. Velikovsky CA, Cassataro J, Sanchez M, et al. Single-shot plasmid DNA intrasplenic immunization for the production of monoclonal antibodies. Persistent expression of DNA. J Immunol Methods. 2000 Oct 20;244(1-2): 1-7.
11. Moonsom S, Khunkeawla P, Kasinrerk W. Production of polyclonal and monoclonal antibodies against CD54 molecules by intrasplenic immunization of plasmid DNA encoding CD54 protein. Immunol Lett. 2001 Feb 1;76(1):25-30.
12. Kasinrerk W, Moonsom S, Chawansuntati K. Production of antibodies by single DNA immunization: comparison of various immunization routes.Hybrid Hybridomics. 2002 Aug;21(4):287-93.
13. Jiao S, Williams P, Berg RK, et al. Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther 1992;3:21 -33.
14. Davis HL, Whalen RG, and Demeneix BA. Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum Gene Ther 1993;4:151 - 159.
15. Major ME, Vitvitski L, Mink MA, et al. DNA-based immunization with chimeric vectors for the induction of immune responses against the hepatitis C virus nucleocapsid. J Virol 1995;69:5798 - 5805.
16. Bohm W, Kuhrober A, Paier T, et al. DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection. J Immunol Methods 1996;193:29-40.
17. Gray D, and Skarvall H: B cell memory is short-lived in the absence of antigen. Nature 1988;336:70-73.
18. Wang B, Boyer J, Srikantan V, et al. DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates. DNA Cell Biol 1993;12:799-805.
19. Takashima A, and Morita A. Dendrictic cells in genetic immunization.J Leukoc Biol 1999;66:350-356.
20. Qian M, Chen S, Li X, et al. Cloning and expression of human UDP-glucuronosyltransferase 1A4 in Bac-to-Bac system. Biochem. Biophys.Res. Commun, 2004,319(2): 386-92.
21. OuelletteT, Destrau S, OuelletteT, et al. Production and purification of refolded recombinant human IL-7 from inclusion bodies. Protein Expr Purif. 2003 Aug;30(2): 156-66.
22. Richter W, Hermsdorf T, Kronbach T, et al. Refolding and purification of recombinant human PDE7A expressed in Escherichia coli as inclusion bodies. Protein Expr Purif. 2002 Jun;25(1):138-48.
23. Margetts MB, Barr IG, Webb EA. Overexpression, purification, and refolding of a Porphyromonas gingivalis cysteine protease from Escherichia coli. Protein Expr Purif. 2000 Apr;18(3):262-8.
24. Stoscheck, CM. Quantitation of Protein. Methods in Enzymology.1990;182: 50-69.
25. Zhang, X., Wang, M., Zhou, C., et al. The expression of iASPP in acute leukemias. Leuk Res. 2005:29,179-83.
1.Sullivan A, Lu X. ASPP: a new family of oncogenes and tumour suppressor genes. Br J Cancer. 2007 Jan 29;96(2):196-200. Epub 2007 Jan 9. Review.
2. Liu ZJ, Lu X, Zhong S. ASPP—Apoptotic specific regulator of p53. Biochim Biophys Acta. 2005 Sep 25;1756(1):77-80. Review.
3. Samuels-Lev Y, O'Connor DJ, Bergamaschi D, et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001; 8:781-794.
4. Gorina, S. & Pavletich N. P. (1996). Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science.274, 1001-5.
5. Bergamaschi, D., Samuels, Y., Jin, B., et al. ASPP1 and ASPP2: common activators of p53 family members. 2004;Mol Cell Biol. 24,1341-50.
6. Yang, J.P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999;274,15662-70.
7. Bergamaschi, D., Samuels, Y., O'Neil, N.J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33,162-7.
8. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.Oncogene. 2004;23, 9007-16.
9. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53.J Mol Biol.2007 May 11;368(4):1162-71.
10.李圣爱。p21WAF1/CIP1基因上游主要转录调控序列区及其相关功能。医学分子生物学杂.2001;23(2):70-74.
11.Koutsodontis G,Tentes I,Papakosta P,et al.Spl plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cipl) gene by the p53 tumor suppressor protein.J Biol Chem.2001 Aug 3;276(31):29116-25.Epub 2001 May 30.
12.Takada N,Sanda T,Okamoto H,et al.RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Spl actions.J Virol.2002 Aug;76(16):8019-30.
13.Kathryn E.Boyd and Peggy J.Farnham.Coexamination of Site-Specific Transcription Factor Binding and Promoter Activity in Living Cells.Mol.Cell.Biol.1999;19:8393-8399.
14.Shang Y,Hu X,DiRenzo J,et al.Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.Cell.2000 Dec 8;103(6):843-52.
15.Yin D,Ong JM,Hu J,et al.Suberoylanilide hydroxamic acid,a histone deacetylase inhibitor:effects on gene expression and growth of glioma cells in vitro and in vivo.Clin Cancer Res.2007 Feb 1;13(3):1045-52
16.Myzak MC,Karplus PA,Chung FL,et al.A novel mechanism of chemoprotection by sulforaphane:inhibition of histone deacetylase.Cancer Res.2004 Aug 15;64(16):5767-74.
17.Kondo Y,Issa JP.Enrichment for histone H3 lysine 9 methylation at Alu repeats in human ceils.J Biol Chem.2003 Jul 25;278(30):27658-62. Epub 2003 Apr 30.
18. Milutinovic S, Brown SE, Zhuang Q, et al. DNA methyltransferase 1 knock down induces gene expression by a mechanism independent of DNA methylation and histone deacetylation. J Biol Chem. 2004 Jul 2;279(27):27915-27. Epub 2004 Apr 15.
19. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al.Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004 Feb 13;303(5660):1010-4.
20. Yin Y, Tainsky MA, Bischoff FZ, et al. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992 Sep 18;70(6):937-48.
21. Kastan MB, Zhan Q, el-Deiry WS, et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71 (4):587-97. )
22. Harper JW, Adami GR, Wei N, et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of Gl cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805-16.
23. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701-4.
24. Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16; 366 (6456) :707-10.
25. Dulic V, Kaufmann WK, Wilson SJ, et al. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced Gl arrest. Cell. 1994 Mar 25;76(6):1013-23.
26. Zhang H, Xiong Y, Beach D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell.1993 Sep;4(9):897-906.
27. Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993 Dec 16; 366 (6456): 707-10.
28. Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor beta responsive elements in the WAFl/Cip1/p21 promoter. J Biol Chem.1995 Dec 1;270(48):28623-8
29. Yamagishi H, Oka T, Nomura H, et al. Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.J Biol Chem. 1997 Aug 29;272(35):22199-206.
30. Sowa Y, Orita T, Minamikawa S, et al .Histone deacetylase inhibitor activates the WAFl/Cipl gene promoter through the Spl sites. Biochem Biophys Res Commun. 1997 Dec 8;241 (1):142-50.
31. Lee SJ, Ha MJ, Lee J, et al. Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAFl/CIPl) in human prostate carcinoma cells. J Biol Chem. 1998 Apr 24;273(17):10618-23.
32. Prowse DM, Bolgan L, Molndr A, et al. Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in keratinocyte differentiation. J Biol Chem. 1997 Jan 10;272(2):1308-14.
33. Biggs JR, Kudlow JE, Kraft AS. The role of the transcription factor Spl in regulating the expression of the WAFl/CIPl gene in U937 leukemic cells. J Biol Chem. 1996 Jan 12;271(2):901-6.
34. Somasundaram K, Zhang H, Zeng YX, et al. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAFl/CiP1.Nature. 1997 Sep 11;389(6647):187-90.
35. Somasundaram K, Zhang H, Zeng YX, et al. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAFl/CiP1.Nature. 1997 Sep 11;389(6647):187-90.
36. Kardassis D, Papakosta P, Pardali K, et al. c-Jun transactivates the promoter of the human p21WAFl/Cipl gene by acting as a superactivator of the ubiquitous transcription factor Spl. J Biol Chem 1999, 274,29572 - 29581.
37. Shao Z., Robbin s P.D. Differential regulation of E2F and Spl-mediated transcription by G1 cyclins. Oncogene. 1995; (19):221-228.
38. Shao Z, Ruppert S, Robbins P. D et al. The retinoblastoma susceptibility gene product binds directly to the human TATA-binding protein-associated factor TAFII250, Proc. Natl. Acad. Sci. USA 92 (1995)3115-3119.
39. Adnane J, Shao Z, P. D. Robbins, et al. Cyclin D1 associates with the TBP-associated factor TAFII250 to regulate Spl-mediated transcription,Oncogene 18 (1999) 239-247
40. Gartel AL, Ye X, Goufman E, et al. Myc represses the p21 (WAFl/CIP1) promoter and interacts with Spl/Sp3. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4510-5. Epub 2001 Mar 27.
41. Mantovani F, Tocco F, Girardini J, et al. The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nat Struct Mol Biol. 2007 Oct;14(10):912-20. Epub 2007 Sep 30.
42. Bergamaschi D, Samuels Y, Sullivan A, et al. iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nat Genet. 2006 Oct;38(10): 1133-41. Epub 2006 Sep 10.
43. Trigiante G, Lu X. ASPP [corrected] and cancer. Nat Rev Cancer. 2006 Mar;6(3):217-26. Review. Erratum in: Nat Rev Cancer. 2006 May;6(5):414.
44. Naumovski L, Cleary ML. The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell cycle progression at G2/M. Mol Cell Biol 1996;16: 3884-3892.
45. Ao Y, Rohde LH, Naumovski L. p53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis. Oncogene. 2001 May 10;20(21):2720-5.
46. Tidow H, Veprintsev DB, Freund SM, et al. Effects of oncogenic mutations and DNA response elements on the binding of p53 to p53-binding protein 2 (53BP2). J Biol Chem. 2006 Oct 27;281(43):32526-33. Epub 2006 Aug 2.
47. Yang JP, Hori M, Takahashi N, et al. NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene. 1999; 18:5177-5186.
48. Helps NR, Barker HM, Elledge SJ, et al. Protein phosphatase 1 interacts with p53BP2, a protein which binds to the tumour suppressor p53. FEBS Lett 1995; 377: 295-300.
49. Espanel X, Sudol M. Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. J Biol Chem. 2001;276:14514-14523.
50. Nakagawa H, Koyama K, Murata Y, et al. APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor,binds to p53-binding protein2 and translocates it to the perinucleus.Cancer Res. 2000; 60: 101-105.
51. Cao Y, Hamada T, Matsui T, et al. Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. Biochem Biophys Res Commun. 2004; 315: 788-795.
52. Bell HS, Dufes C, O'Prey J, et al. A p53-derived apoptotic peptide derepresses p73 to cause tumor regression in vivo. J Clin Invest. 2007 Apr;117(4):1008-18. Epub 2007 Mar 8.
53. Aoyama N, Nagase T, Sawazaki T, et al. Overlap of the p53-responsive element and cAMP-responsive element in the enhancer of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1992 Jun 15; 89 (12) : 5403-7.
1. Linzer DI, Levine AJ. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43-52.
2. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261-3..
3. Jenkins JR, Rudge K, Currie GA. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13-19;312(5995):651-4.
4. Mowat M, Cheng A, Kimura N, et al. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985 Apr 18-24;314(6012):633-6.
5. Chen PL, Chen YM, Bookstein R, et al. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576-80.
6. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature.1992 Mar 19;356(6366):215-21.
7. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233-8.
8. Caron de Fromentel C, Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1—15. Review.
9. Bert Vogelstein, David Lane and Arnold J. Levine. Surfing the p53 network. Nature, 2000,408:307-310.
10. Wolf, D., Harris, N., Goldfinger, N., and Rotter, V. 1985. Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. Mol. Cell. Biol. 5: 127-132.
11. Flaman, J.-M., Waridel, F., Estreicher, A., et al. The human tumor suppressor gene p53 is alternatively spliced in normal cells. 1996.Oncogene 12: 813-818.
12. Courtois, S., Verhaegh, G., North, S., et al. N-p53, a natural isoform of p53 lacking the first transactivation omain, counteracts growth suppression by wild-type p53. Oncogene. 2002;21: 6722-6728.
13. Yin, Y., Stephen, C. W., Luciani, M. G., et al. p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. 2002. Nat. Cell Biol. 4: 462-467.
14. Ghosh, A., Stewart, D., and Matlashewski, G. Regulation of human p53 activity and cell localization by alternative splicing. 2004. Mol. Cell.Biol. 24: 7987-7997
15. Bourdon JC, Fernandes K, Murray-Zmijewski F, et al.p53 isoforms can regulate p53 transcriptional activity. 2005. Genes Dev 19: 2122-2137.
16. Hussain SP, Harris CC. p53 mutation spectrum and load: the generation of hypotheses linking the exposure of endogenous or exogenous carcinogens to human cancer. Mutat Res. 1999 Jul 16;428 (1-2):23-32. Review.
17. El-Deiry, W. S., Kern, S.E., et al. Definition of a consensus binding site for p53. Nat Genet. 1992;1:45-9.
18. Funk, W. D., Pak, D. T., Karas, R. H., et al. A transcriptionally active DNA-binding site for human p53 protein complexes. Mol Cell Biol.1992;12:2866-71.
19. Foster BA, Coffey HA, MorinMJ, et al. Pharmacological rescue of mutant p53 conformation and function. Science. 1999 Dec 24;286(5449):2507-10.
20. Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer. 2004 Oct;4(10):793-805. Review.
21. Moll UM, Erster S, Zaika A. p53, p63 and p73—solos, alliances and feuds among family members. Biochim Biophys Acta. 2001 Dec 28;1552(2):47-59. Review.
22. Kaghad M, Bonnet H, Yang A, et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809-19.
23. Flores ER, Tsai KY, Crowley D, et al. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature. 2002 Apr 4;416(6880): 560-4.
24. Okada Y, Osada M, Kurata S, et al. p53 gene family p51 (p63)-encoded,secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation. Exp Cell Res. 2002 Jun 10;276(2):194-200.
25. Senoo M, Tsuchiya I, MatsumuraY, et al. Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human squamous cell carcinomas:expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51. Br J Cancer. 2001 May 4;84(9):1235-41.
26. Dumaz N, Milhe DM, Meek DW. Protein Kinase CK1 is a p53 threonine-18 Kinase which requires prior phosphorylation of serine 15. FEBS Lett ,1999 ,463 :312-316.
27. Hirao A, Kong YY, Matsuoka S, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000 Mar 10;287(5459):1824-7.
28. Banin S, Moyal L, Shieh S, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998 Sep 11;281(5383):1674-7.
29. Canman CE, Lim DS, Cimprich KA, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 1998 Sep 11;281(5383): 1677-9.
27. Momand, J., Zambetti, G. P., Olson, D. C., George, D., and Levine,A. J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69: 1237-1245, 1992.
28. Wu, L. and Levine, A. J. Differential regulation of the p21/WAF-1 and MDM2 genes after high-dose UV irradiation: p53-dependent and p53-independent regulation of the MDM2 gene. 1997, Mol. Med., 3: 441 -451.
29. Barak, Y., Juven, T., Haffner, R., and Oren, M. The MDM2 expression is induced by wild type p53 activity. 1993, EMBO J., 12: 461-468.
30. Chen, J., Marechal, V., and Levine, A. J. Mapping of the p53 and mdm-2 interaction domains. 1993, Mol. Cell. Biol., 13: 4107-4114.
31. Picksley, S. M. and Lane, D. P. The p53-MDM2 autoregulatory feedback loop: a paradigm for the regulation of growth control by p53? BioEssays.1993; 15: 689-690.
32. Haupt, Y., Maya, R., Kazaz, A., et al. MDM2 promotes the rapid degradation of p53. Nature, 1997;387: 296-299.
33. Kubbutat, M. H., Jones, S. N., and Vousden, K. H. Regulation of p53 stability by MDM2. Nature. 1997;387: 299-303.
34. Bottger, A., Bottger, V., Sparks, A., Liu, W. L., Howard, S. F., and Lane, D. P. Design of a synthetic MDM2-binding mini protein that activates the p53 response in vivo. Curr. Biol. 1997;7:860 - 869.
35. Maki, C. G. Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2. J. Biol. Chem. 1999; 274: 16531-16535.
36. Shirangi, T. R., Zaika, A., and Moll U. M. Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage.2002. FASEB J., 16: 420-422.
37. Lavin MF, Gueven N. The complexity of p53 stabilization and activation.Cell Death Differ. 2006 Jun;13(6):941-50. Review.
38. Lev Bar-Or R, Maya R, Segel LA, et al. Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11250-5.
39. Buschmann T, Fuchs SY, Lee CG, et al. SIMM modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell. 2000 Jun 23;101(7):753-62.
40. Zhang Y, Xiong Y. Control of p53 ubiquitirmtion and nuclear export bv MDM2 and ARF. Cell Growth Difer, 2001, 12(4): 175-186.
41. Tolbert D, Lu X, Yin C, et al. p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo. Mol Cell Biol. 2002 Jan;22(1):370-7.
42. Xirodimas D, Saville MK, Edling C, et al. Different effects of pHARF on the levels of ubiquitinated p53 and Mdm2 in vivo. Oncogene. 2001 Aug 16; 20 (36): 4972-83.
43. Ho GH, Calvano JE, Bisogna M, et al. Genetic alterations of the pl4ARF-hdm2-p53 regulatory pathway in breast carcinoma. Breast Cancer Res Treat.2001 Feb;65(3):225-32.
44. Su JD, MAYO LD, DONNER DB, et al. PTEN and phosphatidylinositol 3'-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment. Cancer Res, 2003, 63(13):3585-3592.
45. OGAWARA Y, KISHISHITA S, OBATA T, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem, 2002, 277(24): 21843-21850.
46. YAN X, FRASERM, QIU Q, et al. Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a P53-dependent manner. Gynecol Oncol , 2006,102 (2):348-355.
47. CHANG CJ, FREEMAN DJ, WU H. PTEN regulates Mdm2 expression through the P1 promoter. J Biol Chem, 2004, 279(28):29841-29848.
48. FREEMAN DJ, LI AG, WEI G, et al. PTEN tumor suppressor regulates P53 protein levels and activity through phosphatase-dependent and-independent mechanisms [J]. Cancer Cell, 2003, 3(2):117-130.
49. OKUMURA K, ZHAO M, DEPINHO RA, et al. PTEN: a novel anti-oncogenic function independent of phosphatase activity. Cell Cycle, 2005,4(4):540-542.
50. PAEZ J, SELLERS WR. PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res, 2003, 115:145-167.
51. KOMAZAWA N, SUZUKI A , SANO S, et al. Tumorigenesis facilitated by Pten deficiency in the skin : Evidence of P53-Pten complex formation on the initiation phase. Cancer Sci,2004, 95(8) :639 - 643.
52. TANG Y, ENG C. PTEN autoregulates its expression by stabilization of p53 in a phosphatase-independent manner. Cancer Res, 2006,66:736-742.
53. STAMBOLIC V, MACPHERSON D, SAS D, et al. Regulation of PTEN transcription by P53. Mol Cell, 2001, 8(2):317-325.
54. WANG J, OUYANG W, LI J, et al. Loss of tumor suppressor p53 decreases PTEN expression and enhances signaling pathways leading to activation of activator protein 1 and nuclear factor kappaB induced by UV radiation.Cancer Res, 2005, 65(15):6601 -6611.
55. Garkavtsev I, Grigorian IA, Ossovskaya VS, et al. The candidate tumour suppressor p33INGl cooperates with p53 in cell growth control. Nature.1998 Jan 15;391(6664):295-8.
56. Zhang Y, Xiong Y. A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science. 2001 Jun 8;292(5523):1910-5.
57. Shaw, P., Freeman, J., Bovey, R. & Iggo, R. Regulation of specific DNA binding by p53: evidence for a role for O-glycosylation and charged residues at the carboxy-terminus. Oncogene. 1996; 12, 921-930.
58. Wesierska-Gadek, J., Bugajska-Schretter, A. & Cerni, C.ADP-ribosylation of p53 tumor suppressor protein: mutant but not wild-type p53 is modified. J. Cell Biochem. 1996; 62:90-101.
59. Gatti, A., Li, H. H., Traugh, J. A. et al. Phosphorylation of human p53 on Thr-55. Biochemistry. 2000;39, 9837-9842.
60. Waterman, M. J., Stavridi, E. S., Waterman, J. L. et al. ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nature Genet. 1998; 19, 175-178.
61. Colman MS , Afshari CA , Barrett JC. Regulation of p53 stability and activity in response to genotoxic stess. Mutat Res , 2000 ; 462 :179-188.
62. Oda K, Arakanca H , Tanaka T , et al. p53AIPl ,a potential mediator of p53 dependent apoptosis , and its regulation by ser-462 phosphorylated p53. Cell , 2000; 102 :8492862.
63. Haneda, M. et al. Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA-damaging stressinduced phospho-serine 15 of p53.FEBS Lett. 2004; 567, 171 - 174.
64. Fan, G., Ma, X., Wong, P. Y., et al. p53 dephosphorylation and p21 (Cipl/Wafl) translocation correlate with caspase-3 activation in TGF-β1-induced apoptosis of HuH-7 cells. Apoptosis. 2004; 9, 211-221.
65. Pluquet O , Hainaut P. Genotoxic and non-genotoxic pathways of p53 induction. Cancer Lett , 2001 ,174 :1-15.
66. Hofmann TG, Möller A , Sirma H , et al . Regulation of p53 activity by its interaction with homeodomain 2 interacting protein kinase-2. Nat Cell Biol. 2002 ,4 : 1-10.
67. Brooks CL, Gu W. p53 ubiquitination: Mdm2 and beyond. Mol Cell. 2006 Feb 3;21(3):307-15. Review.
68. Rodriguez, M. S. et al. SUMO-1 modification activates the transcriptional response of p53. EMBO J. 1999; 18, 6455-6461.
69. Gostissa, M. et al. Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J. 1999; 18, 6462-6471.
70. Melchior, F. & Hengst, L SUMO-1 and p53. Cell Cycle 2002; 1, 245 - 249.
71. Chen, L. & Chen, J. MDM2-ARF complex regulates p53 sumoylation.Oncogene 2003; 22, 5348-5357.
72. Braithwaite AW, Del Sal G, Lu X. Some p53-binding proteins that can function as arbiters of life and death. Cell Death Differ. 2006 Jun;13(6):984-93.
73. Prives C and Hall PA. The p53 pathway. J. Path. 1999; 187: 112-126.
74. Zilfou J, Hoffman WH, Sank M, et al. The corepressor mSin3a interacts with the proline-rich domain of p53 and protects p53 from proteasome mediated degradation. Mol. Cell. Biochem. 2001,21: 3974-3985.
75. Iwabuchi, K., Bartel, P. L., Li, B., et al. Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci U S A.1994;91,6098-102.
76. Gorina, S. & Pavletich N. P. (1996). Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science.274,1001-5.
77. Naumovski, L. & Cleary, M. L. The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell cycle progression at G2/M. Mol Cell Biol. 1996;16,3884-92.
78. Takahashi N, Kobayashi S, Jiang X, et al. Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative splicing. Biochem Biophys Res Commun. 2004 Mar 5;315(2):434-8.
79. Ao Y, Rohde LH, Naumovski L. p53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis. Oncogene. 2001 May 10;20(21):2720~5.
80. Kobayashi S, Kajino S, Takahashi N, et al. 53BP2 induces apoptosis through the mitochondrial death pathway. Genes Cells. 2005 Mar;10(3): 253-60.
81. Cao Y, Hamada T, Matsui T, et al. Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. Biochem Biophys Res Commun. 2004 Mar 19;315(4):788-95.
82. Yang JP, Hori M, Takahashi N, et al. NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene. 1999 Sep 16;18(37):5177-86.
83. Lopez CD, Ao Y, Rohde LH, et al. Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53. Mol Cell Biol.2000 Nov;20(21):8018-25.
84. Nakagawa H, Koyama K, Murata Y, et al. APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor,binds to p53-binding protein 2 and translocates it to the perinucleus.Cancer Res. 2000 Jan 1;60(1):101-5.
85. Samuels-Lev, Y., O'Connor, D. J., Bergamaschi, D., et al. ASPP proteins specifically stimulate the apoptotic function of p53. 2001; Mol Cell. 8, 781-94.
86. Bergamaschi, D., Samuels, Y., Jin, B., et al. ASPP1 and ASPP2: common activators of p53 family members. 2004;Mol Cell Biol. 24,1341-50.
87. Iwabuchi K, Li B, Massa HF, et al. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. J Biol Chem. 1998 Oct 2;273(40):26061-8.
88. Bergamaschi D, Samuels Y, Zhong S, et al. Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation.Oncogene. 2005 May 26;24(23):3836-41.
89. Fogal V, Kartasheva NN, Trigiante G, et al. ASPP1 and ASPP2 are new transcriptional targets of E2F. Cell Death Differ. 2005 Apr; 12(4):369-76.
90. Liu ZJ, Lu X, Zhang Y, et al. Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53. FEBS Lett. 2005 Mar 14;579(7):1587-90.
91. Yang, J. P., Hori, M., Sanda, T., et al. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. J Biol Chem. 1999;274,15662-70.
92. Bergamaschi, D., Samuels, Y., O'Neil, N. J., et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. 2003; Nat Genet. 33, 162-7.
93. Liu ZJ, Zhang Y, Zhang XB, et al. Abnormal mRNA expression of ASPP members in leukemia cell lines. Leukemia. 2004 Apr;18(4):880.
94. Zhang, X., Wang, M., Zhou, C., et al.The expression of iASPP in acute leukemias. Leuk Res. 2005;29, 179-83.
95. Slee, E. A., Gillotin, S., Bergamaschi, D., et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization. Oncogene. 2004;23, 9007-16.
96. Zhang X, Diao S, Rao Q, et al. Identification of a novel isoform of iASPP and its interaction with p53. J Mol Biol. 2007 May 11; 368(4):1162-71.
97. Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr. Biol. 2007; 17, 1298-1307.
98. Chang TC, Wentzel EA, Kent OA. et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 2007; 26, 745-752.
99. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447, 1130-1134.
100. Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell.2007;26,731-743.
101. Tarasov V, Jung P, Verdoodt B,et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. 2007;Cell Cycle 6,1586 - 1593.
102. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116, 281-297.
103. Zamore, P. D. & Haley, B. Ribo-gnome: the big world of small RNAs.Science 2005;309, 1519- 1524.
104. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene.2007 Jul 26;26(34):5017-22.
105. Zhao R, Gish K, Murphy M, et al. Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 2000 Apr 15;14(8):981-93.
106. Wei, C. L., Wu, Q., Vega, V. B., et al. A GlobalMap of p53 Transcription-Factor Binding Sites in the Human Genome. Cell.2006;124:207-19
107. Fisher DE. The p53 tumor suppressor: critical regulator of life & death in cancer. Apoptosis, 2001, 6(1-2): 7—15.
108. Cory, S. and Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647-656.
109. Nakano K, Vousden KH. PUMA ,a novel proapoptotic gene is induced by p53. Molecular Cell, 2001, 7(3):683-694.
110. Yu J, Zhang L, Hwang PM, et al. PUMA induces the rapid apoptosis of colorectal cancer cell. Molecular Cell, 2001, 7(3):673-682.
111. Han JW, Flemington C, Houghton AB, et al. Expression of bbc3, a pro-apoptotic BH-3only gene,is regulated by diverse cell death and survival signals. Proc Natl Acad Sci U S A, 2001, 98(20): 11318-11323..
112. Oda, E., Ohki, R., Murasawa, H., et al. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.Science 288, 1053-1058.
113. Oda K, Arakawa H, Tanaka T, et al. p53AIPl, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.Cell. 2000 Sep 15;102(6):849-62.
114. Boldin MP, Mett IL, Varfolomeev EE, et al. Self-association of the "death domains" of the p55 tumor necrosis factor (TNF) receptor and Fas/APOl prompts signaling for TNF and Fas/APOl effects. J Biol Chem. 1995 Jan 6; 270(1): 387-91.
115. Shimasaki S, Koba A, Mercado M, et al. Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA. Biochem Biophys Res Commun. 1989 Dec 15;165(2):907-12.
116. Nagata, S. and Golstein, P. (1995). The Fas death factor. Science 267, 1449-1456.
117. Muller, M., Wilder, S., Bannasch, D., Israeli, D., Lehlbach, K.,Li-Weber, M., Friedman, S. L., Galle, P. R., Stremmel, W., Oren, M. et al. (1998). p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J. Exp. Med. 188, 2033-2045.
118. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004 Feb 13;303(5660):1010-4.
119. Wahl GM, Linke SP, Paulson TG, et al. Maintaining genetic stability through TP53 mediated checkpoint control. Cancer Surv. 1997; 29:183 - 219.
120. Cheung KJ Jr, Mitchell D, Lin P, et al.The tumor suppressor candidate p33(INGl) mediates repair of UV-damaged DNA. Cancer Res. 2001 Jul 1;61(13):4974-7.
121. Kaina B. DNA damage—triggered apoptosis: critical role of DNA repair, double strand breaks, cell proliferation and signaling. Biochem Pharmacol, 2003, 66(8): 1547-1554)c
122. Schwarte-Waldhoff I, Volpert 0V, Bouck NP, et al. Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9624-9.
123. Yu JL, Rak JW , Comber BL, et al. Efect of p53 status on tumor response to antiangiogenic therapy. Science, 2002; 295: 1526-1528.
124. Aranda-Anzaldo A, Dent MA. Developmental noise, ageing and cancer. Mech Ageing Dev. 2003 Jun;124(6):711-20. Review.
125. Xu L, Pirollo KF,Tang WH, et al. Transferrin-liposome mediate systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum Gene Ther, 1999; 10: 2941-2952.
126. Foster BA, Cofey HA, Morin MJ, et al. Pharmacological rescue of mutant p53 conformation and funetion. Science. 1999, 286(549):2507-2510
127. Bullock AN, Fersht AR. Rescuing the function of mutant p53. Nat Rev Cancer. 2001, 1(1): 68—76.) .
128. Bottger A, Bottger V, Sparks A, et al. Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo. Curr Biol, 1997;7(11): 860-869.
129. O'Keefe K, Li H, Zhang Y.Nucleocytoplasmic shuttling of p53 is essential for MDM2-mediated cytoplasmic degradation but not ubiquitination.Mol Cell Biol. 2003 Sep;23(18):6396-405.
130. Almog N, Rotter V. An insight into the life of p53: a protein coping with many functions! Review of the 9th p53 Workshop, Crete, May 9-13, 1998.Biochim Biophys Acta. 1998 Nov 26;1378(3):R43-54.
131. Chang EH, Pirollo KF, Bouker KB, et al. Tp53 gene therapy: a key to modulating resistance to anticancer therapies? Mol Med Today,2000, 6(9): 358-364.
132. Swisher SG, Roth JA. Clinical update of Ad-p53 gene therapy for lung cancer. Surg Oncol Clin N Am, 2002, 11(3):521-535.
133. Braithwait A. W and Prives C. L. p53: more research and more questions.Cell Death and Differentiation (2006) 13, 877-880.
134. Bourdon J. C, Laurenzi V. De, Melino G et al. p53: 25 years of research and more questions to answer. Cell Death and Differentiation (2003) 10,397 - 399.
135. Jegga AG, Inga A, Menendez D, Aronow BJ, Resnick MA. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):944-9. Epub 2008 Jan 10.