VD_3、9-cis RA及其受体对hsp90β基因转录的调控机制及GA对VDR、RXR表达水平和反式调控活性的影响
摘要
Hsp90是细胞中一类含量丰富的胞浆蛋白，作为一种分子伴侣参与细胞对各种刺激的保护性反应和信号传导、细胞周期调控、激素应答等广泛的生理过程。Hsp90可以与GR等类固醇激素受体结合，使其保持稳定状态，并且是其与配体结合的先决条件，但目前尚未发现VDR、TR、RAR等非激素受体与Hsp90呈结合状态。Hsp90与CDC37形成复合物可以稳定Cdk4，从而间接参与细胞周期调控；GA作为一种抗肿瘤药物可以特异结合Hsp90，并抑制其功能，提示Hsp90在细胞生长过程中发挥重要作用。
VD_3除了可以调控人体钙磷代谢外，还具有其他多种生理功能，尤其是具有促细胞分化功能，似乎与Hsp90对细胞周期的影响相反。因此研究VD_3及其受体与Hsp90之间是否存在相互调节关系，将为进一步探讨Hsp90在细胞生长方面或其他方面的功能提供线索。
人类hsp90基因在细胞中有两个拷贝，即hsp90α、hsp90β，二者有很高序列同源性，但具有不同的调控机制。本组以往的研究表明，hsp90β基因第一内含子在该基因的高组成性和热诱导表达中起重要作用，而其中含有与人骨钙素基因调控序列中相同的VD_3应答元件(VDRE)样序列，GGGTGA(N)_(10)GGGTGA(+233bp／+254bp)。VDR作为核受体家族的成员，通常与RXR形成异源二聚体结合于靶基因VDRE上，介导VD_3的转录调控功能，此过程还需要一些辅助因子的参与。本论文对hsp90β基因中该位点是否介导VD_3及其受体参与hsp90β基因的表达调控及其调控机制进行了研究。
一、VD_3和9-cis RA对hsp90β基因的转录调控作用
为了解VD_3对hsp90β基因的转录调控作用，我们将hsp90β基因上游全长调控序列(-1039bp／+1531bp)介导的荧光素酶(Luc)报告基因质粒β1.11转
Hsp90 is a highly conserved, ubiquitous and abundant molecular chaperon with essential roles in stress tolerance and protein folding. In eukaryocytes, cytoplasmic Hsp90s act as specific chaperone for nuclear receptors, kinases and transcription factors. Hsp90 may be required to maintain certain nuclear receptors, such as GR, PR, ER and so on, in a potential state that functions to promote ligand binding, nuclear transportation and provide higher affinity to hormone response elements. However no direct evidence has yet been shown on the formation of stable complex between Hsp90 and VDR, TR or RXR family. Hsp90/CDC37 complex has also been shown to stabilize Cdk4 and participate indirectly in cell cycle procession. Geldanamycin (GA), known as candidate drugs for tumor chemotherapy, specifically binds to Hsp90 and inhibits at least part of its function. The phenomena aforementioned suggest that Hsp90 exert important function in cell growth.
VD_3 exerts a lot of physiological functions beyond the bone mineral homeostasis realm, especially in stimulating cell differentiation, which seems to be rather contradictory to the function of Hsp90 in cell cycle procession. We are thus interested to know whether there are some regulatory interactions between them, and this study perhaps will provide some more clues for Hsp90's function on cell cycle progression.
We have reported elsewhere about the important function of the first intron of hsp90P on its constitutive and heat inductive expression, in which an intronic VD_3
VD_3除了可以调控人体钙磷代谢外，还具有其他多种生理功能，尤其是具有促细胞分化功能，似乎与Hsp90对细胞周期的影响相反。因此研究VD_3及其受体与Hsp90之间是否存在相互调节关系，将为进一步探讨Hsp90在细胞生长方面或其他方面的功能提供线索。
人类hsp90基因在细胞中有两个拷贝，即hsp90α、hsp90β，二者有很高序列同源性，但具有不同的调控机制。本组以往的研究表明，hsp90β基因第一内含子在该基因的高组成性和热诱导表达中起重要作用，而其中含有与人骨钙素基因调控序列中相同的VD_3应答元件(VDRE)样序列，GGGTGA(N)_(10)GGGTGA(+233bp／+254bp)。VDR作为核受体家族的成员，通常与RXR形成异源二聚体结合于靶基因VDRE上，介导VD_3的转录调控功能，此过程还需要一些辅助因子的参与。本论文对hsp90β基因中该位点是否介导VD_3及其受体参与hsp90β基因的表达调控及其调控机制进行了研究。
一、VD_3和9-cis RA对hsp90β基因的转录调控作用
为了解VD_3对hsp90β基因的转录调控作用，我们将hsp90β基因上游全长调控序列(-1039bp／+1531bp)介导的荧光素酶(Luc)报告基因质粒β1.11转
Hsp90 is a highly conserved, ubiquitous and abundant molecular chaperon with essential roles in stress tolerance and protein folding. In eukaryocytes, cytoplasmic Hsp90s act as specific chaperone for nuclear receptors, kinases and transcription factors. Hsp90 may be required to maintain certain nuclear receptors, such as GR, PR, ER and so on, in a potential state that functions to promote ligand binding, nuclear transportation and provide higher affinity to hormone response elements. However no direct evidence has yet been shown on the formation of stable complex between Hsp90 and VDR, TR or RXR family. Hsp90/CDC37 complex has also been shown to stabilize Cdk4 and participate indirectly in cell cycle procession. Geldanamycin (GA), known as candidate drugs for tumor chemotherapy, specifically binds to Hsp90 and inhibits at least part of its function. The phenomena aforementioned suggest that Hsp90 exert important function in cell growth.
VD_3 exerts a lot of physiological functions beyond the bone mineral homeostasis realm, especially in stimulating cell differentiation, which seems to be rather contradictory to the function of Hsp90 in cell cycle procession. We are thus interested to know whether there are some regulatory interactions between them, and this study perhaps will provide some more clues for Hsp90's function on cell cycle progression.
We have reported elsewhere about the important function of the first intron of hsp90P on its constitutive and heat inductive expression, in which an intronic VD_3
引文
沈珝琲，方福德主编．1997，真核基因表达调控．
王艳林，沈珝诽，梅树恩，莫显明，刘巨洪，吴宁华．1996，科学通报，18：1699-1702
Bernd S and Ulrich G. 1997, The function of steroid horone receptors is inhibited by the hsp90-specific compound geldanamycin. J. Biol. Chem., 272:18694-18701
Bohen SP and Yamamoto KR. 1993, Isolation of Hsp90 mutants by screening for decreased steroid receptor function. Proc. Natl. Acad. Sci. USA, 90:11424-11428
Bresnick EK, Dalman FC, Sanchez ER and Pratt WB. 1989, Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. J. Biol. Chem., 264:4992-4997
Brugge JS, Erikson E and Erikson RL. 1981, The specific interaction of the Rous Sarcoma virus transforming protein pp60src, with two cellular proteins. Cell, 25: 363-372
Bugge TH, Pohl J, Lonnoy O and Stunnenberg HG. 1992, RXRα, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J, 11:1409-1418
Casteels K, Bouillon R, Waer M and Mathieu C. 1995, Immunomodulatory effects of VD3. Curr. Opin. Nephrol. Hypertens., 4:313-318
Chen CF, Chen Y, Dai K, Chen PL, Riley DJ and Lee WH. 1996, A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. Mol. Cell. Biol., 16:4691-4699
Chen JD and Evans RM. 1995, A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature, 377:454-457
Craig TA, Lutz WH and Kumar R. 1999, Association of prokaryotic and eukaryotic chaperone proteins with the human 1α,25-dihydroxyvitamin D3 recepor. Biochem. Biophy. Res. Commun., 260:446-452Dai K, Kobayashi R and Beach D. 1996, Physical interaction of mammalian CDC37 with CDK4. J. Biol. Chem., 271: 22030-22034
Dalman FC, Ronald JK, Perdew GH, Massa E and Pratt WB. 1990, In contrast to the glucocorticoid receptor, the thyroid hormone receptor is translated in the DNA binding state and is not associated with hsp90. J. Biol. Chem., 265: 3615-3618
Dalman FC, Sturzenbecker LJ, Levin aa, Lucas DA, Perdew GH, Petkovitch M, Chambon P, Grippo JF and Pratt WB. 1990, Retinoid acid receptor belongs to a subclass of nuclear receptors that do not form "docking" complexes with hsp90. Biochemistry, 30: 5605-5608
Edmondson DG, Roth SY. 1996, Chromatin and transcription. FASEB J, 10: 1173- 1182
Forman BM, Umesono K, Chen J and Evans RM. 1995, Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell, 81: 541-550
Freedman LP. 1999, Increasing the complexity of coactivation in nuclear receptor signaling. Cell, 97:5-10
Hartl FU. 1996, Molecular chaperones in cellular protein folding. Nature, 381: 571- 580
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, Dominguez CE and Jurutka PW. 1998, The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J. Bone Mineral Res., 13:325-349
Heads RJ, Yellon DM and Latchman DS. 1995, Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells. J. Mol. Cell. Cardiol., 27: 1669-1678
Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L. 1996, Nuclear receptor coactivators and corepressors. Mol Endocrinol, 10: 1167-1177Hunter T and Poon RYC. 1997, Cdc37: a protein kinase chaperone? Trends Cell Biol.,7: 157-161
Jakob U, Lilie H, Meyer I and Buchner J. 1995, Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo. J. Biol. Chem., 270: 7288-7294
June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF and Samuelson LE. 1990, Inhibition of tyrosine phosphorylation prevents T-cell receptor- mediated signal transduction. Proc. Natl. Acad. Sci. USA, 87: 7722-7726
Kang KI, Devin J, Cadepond F, Jibard N, Guiochon-Mantel A, Baulieu EE and Catelli MG. 1994, In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus. Proc. Natl. Acad. Sci. USA, 91: 340-344
Kavva S, Nikaido T, Aoki Y, Zhai Y, Kumagai T, Furihata K, Fujii S, Kiyosawa K. 1997, Vitamin D analogues up-regulate p21 and p27 during growht inhibition of pancreatic cancer cell lines. Br. J. Cancer, 76: 884-889
Kliewer SA, Umesono K, Mangelsdorf DJ and Evans RM. 1992 (a), Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D_3 signalling. Nature, 355: 446-449
Kliewer SA, Umesono K, Noonan DJ, Heyman RA and Evans RM. 1992 (b), Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature, 358: 771-774
Kurokawa R, DiRenzo J, Boehm M, Sugarman J, Gloss B, Rosenfeld MG, Heyman RA and Glass CK. 1994, Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature, 371, 528-531
Luisi BF, Xu W, Otwinowski Z, Freedman LP, Yamamoto KR and Sigler PB. 1991, Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA .??Natrue (London) 352: 497-505
Marks MS, Hallenbeck PL, Nagata T, Segars JH, Appella E, Nikodem VM and Ozato K. 1992, H-2RIIBP (RXRp) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J, 11: 1419-1435
Mayer MP and Bernd Bukau. 1999, Current Biol., 9: R322-R325
Mendel DB and Orti E. 1988, Isoform composition and stoichiometry of the 90 kDaheat shock protein associated with glucocorticoid receptors J. Biol. Chem., 263: 6695-6702
Miyata U and Yahara I. 1995, Interaction between casein kinase II and the 90-kDa stress protein, Hsp90. Biochemistry, 34: 8123-8129
Naar AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK and Rosenfeld MG. 1991, The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell, 65: 1267-1279
Nair SC, Toran EJ, Rimerman RA et al. 1996, A pathway of multi-chaperon interactions common to diverse regulatory proteins-estrogen receptor, fes tyrosine kinase, heat shock trascription factor, HSF1, and the aryl hydrocarbon receptor. Cell Stress Chaperones, 1: 237-250
Nathan DF, Vos MH and Lindquist S. In vivo functions of the Saccharomyces cerevisiae hsp90 chaperone. Proc. Natl. Acad. Sci. USA, 94: 12949-12956
Naveilhan P, Nevey I, Wion D and Brachet P. 1996, 1,25-dihydroxyvitamin D3, and inducer of glial cell line-derived neurotrophic factor. Neuroreport, 7:2171-2175
O'Connell TD, Simpson RU. 1995, 1,25-dihydroxyvitamin D3 regulation of myocardial growth and c-myc levels in the rat heart. Biochem Biophys Res Commun, 213: 59-65
Perlmann T and Evans RM. 1997, Nuclear receptors in Sicily: All in the famiglia.??Cell, 90: 391-397
Pratt WB. 1997, The role of the hsp90-based chaperone system in signal transduction by nuclear receptor and receptors signaling via MAP kinase. Annu. Rev. Pharmacol. Toxicol., 37: 297-326
Pratt WB and Toft DO. 1997, Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr. Rev., 18: 306-360
Rutherford SL, Lindquist S: Hsp90 as a capacitor for morphological evolution. Nature, 396: 336-342
Sambrook J, et al. 1989, Molecular cloning, A laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press.
Selden, RF. Transfection using DEAE-Dextran. In: Ausubel, FM, Brent R, Kinston RE, eds. Current protocol in molecular biology, 3rd ed. New York: John Wiley & Sons Inc., 1987.9-9-9-11
Sepehrnia B, Paz IB, Dasgupta G and Momand J. 1996, Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell. J. Biol. Chem., 271: 15084-15090
Shen YF, Liu JH, Wang XZ, Wu NH. 1997, Essential roles of first intron in transcription regulation of hsp90β gene. FEBS letters, 413: 92-96
Shen YF and Wen GY. 1999, Adv. Med. Mol. Biol., 2: 205-208
Simboli-Campbell M, Narvaez CJ, van Weelden K, Tennis-wood M and Welsh J. 1997, Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells. Cancer Res Treat, 42: 31-41
Smith DF and Toft DO. 1993, Steroid recptors and their associated proteins. Mol. Endocrinol., 7: 4-11
Stancato LF, Chow YH, Hutchison KA, Perdew GH, Jove R and Pratt WB. 1993, Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a??cell-free system. J. Biol. Chem., 268: 21711-21716
Stancato LF, Silverstein AM, Owens-Grillo JK, Chow YH, Jove R and Pratt WB. 1997, The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of Raf kinase. J. Biol. Chem., 272: 4013-4020
Stepanova L, Leng XH, Parker SB and Harper JW. 1996, Mammalian p50~(cdc37) is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev., 10: 1491-1502
Trent JD, Kagawa HK, Yaoi T, Olle E and Zaluzec NJ. 1997, Chaperonin filaments: the archaeal cytoskeleton? Prox Natl. Acad Sci. USA, 94: 5383-5388
Uehara Y, Murakami Y, Mizuno S and Kawai. 1988, Inhibition of transforming activity of tyrosine kinase oncogenes by herbimycin A. Virology, 164: 294-298
Umesono K, Murakami KK, Thompson CC and Evans RM. 1991, Direct repeats as selective response elements for the thyroid hormone, retioic acid and vitamin D3 receptors. Cell, 65: 1255-1266
Whitesell L, Mimnaugh EG, De Costa B, Myers CE and Neckers LM. 1994, Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA, 91: 8324-8328
Xiao L, Lang WH. A dominant role for the c-jun NH2-terminal kinase in oncogenic Ras-induced morphologic transformation of human lung carcinoma cells. Cancer Res, 2000, 60: 400-408
Yahara I, Iida H and Koyasu S. 1986, A heat shock-resistant variant of Chinese hamster cell line constitutively expressing heat shock protein of Mr 90,000 at high level. Cell Struct. Funct., 11: 65-73Yonehara M, Minami Y, Kawata Y, Nagai J and Yagara I. 1996, Heat-induced chaperone activity of HSP90. J. Biol. Chem., 271: 2641-2645
Yu VC, Delsert C, Andersen B, Holloway M, Naar AM, Kim SY, Boutin JM, Glass CK and Rosenfeld M. 1991, RXRβ: a coregulator that enhances binding of retinoic acid, thyroid hormone and vitamin D receptors to their cognate response elements. Cell, 67: 1251-1266
Zhang XK, Hoffmann B, Tran PBV, Graupner G and M Pfahl 1992, Retinoid X receptor is an auxiliary protein for thyroid hormones and retioic acid receptors. Nature (London), 355: 441-4461. Tsai MJ et al. Annu Rev Biochem, 1994, 63:451-86
2. Lemon BD, Freedman LP. Nuclear receptor cofactors as chromatin remodelers. Curr Opin Genet Dev, 1999, 9:499-504
3. Leid M, Kastner P, Chambon P. Trends Biochem Sci, 1992,17:427-433
4. Chambon P. FASEB J, 1996,10:940-954
5. Nagpal S, Saunders M, Kastner Pet al. Cell, 1992, 70:1007-1019
6. Nagpal S, Friant A, Chambon P et al. EMBO J, 1993, 12:2349-2360
7. Glass CK, Rose DW, Rosenfeld MG. Nuclear receptor coactivators. Curr Opin Cell Biol, 1997, 9:222-232
8. Moras D, Gronemeyer H. Curr Opin Cell Biol, 1998, 10:384-391
9. Mangelsdorf DJ et al. Cell, 1995, 83:835-839
10. Cooney AJ et al. Biochem Biophys Res Commun, 1998, 245 (1): 94-100
11. Pratt WB. Annu Rev Pharmacol Toxicol, 1997, 37:297-326
12. Freedman LP. Increasing the complexity of coactivation in nuclear receptor signaling. Cell, 1999,97:5-8
13. Adams CC, Workman JL. Nucleosome displacement in transcription. Cell, 1993, 72:305-308
14. Beato M, Sanchez-Pacheco A. Interaction of steroid hormone receptors with the transcription initiation complex. Endocr Rev, 1996, 17:587-609
15. Schwerk C, Klozbucher M, Sachs M, Ulber Vet al. Identification of a??transactivation function in the progesterone receptor that interacts with the TAFII 110 subunit of the TFIID complex. J Biol Chem, 1995,270: 21331-21338
16. Ford J, McEwan IJ, Wright APH et al. Involvement of the transcription factor IID protein complex in gene activation by the N-terminal transactivation domain of the glucocorticoid receptor in vitro. Mol Endocrinol, 1997, 11: 1467- 1475
17. McEwan IJ, Gustofsson JA. Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF. Proc Natl Acad Sci USA, 1997, 94:8485-8490
18. Tasset D, Tora L, Fromental C et al. Distinct classes of transcriptional activating domains function by different mechanisms. Cell, 1990, 62: 1177-1187
19. Horwitz KB, Jackson TA, Bain DL et al. Nuclear receptor coactivators and corepressors. Mol Endocrinol, 1996, 10: 1167-1177
20. Shibata H, Spencer TE, Onate SA et al. Role of coactivators and corepressors in the mechanism of steroid thyroid receptor action. Recent Prog Horm Res, 1997,52:1-25
21. L'Horset F, Dauvois S, Heery DM et al. RIP-140 interacts with multiple nuclear receptors by means of two distinct sites. Mol Cell Biol, 1996, 11: 6029- 6036
22. Ding XF, Anderson CM, Ma H et al. Nuclear receptor-binding sites of coactivators glucocorticokd receptor interacting protein I (GRIP1) and steroid receptor coactivator 1 (SRC-1): Mutiple motifs with different binding specificities. Mol Endocrinol, 1998, 12:302-313
23. Onate SA, Boonyaratanakornkit V, Spencer TE et al. The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AFl)and AF2??domains of steroid receptors. J Biol Chem, 1998, 273: 12101-12108
24. Voegel JJ, Heine MJS, Tini M et al. The coactivator TIF2 contains three nuclear receptor -binding motifs and mediates transactivation through CBP binding-depengdent and-independent pathways. EMBO J, 1998, 17:507-519
25. Xu L, Glass CK, Rosenfeld MG. Curr Opin Genet Dev, 1999,9:140-147
26. Shiau AK, Barstad D, Loria PM et al. Cell, 1998, 95: 927-937
27. Yeh S, Chang C. Cloning and characterization of a specific coactivator ARA70 for the androgen receptor in human prostate cells. Proc Natl Acad Sci USA, 1996,93:5517-5521
28. Swanson HL, Bradfield CA. The AH-receptor: Genetics structure and function. Pharmacogenetics, 1993, 3:213-230
29. Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol, 1995, 35: 307-340
30. Tsukiyama T, Wu C. Chromatin remodeling and transcription. Genes Dev, 1997, 7: 182-191
31. Getzenberg RH, Pienta KJ, Ward WS et al. Nuclear structure and the three-dimensional organization of DNA. J Cell Biochem, 1991,47: 289-299
32. Wolffe AP, Pruss D. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell, 1996, 86: 817-819
33. Brownell JE, Zhou J, Ranalli T et al. Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell, 1996, 84, 943-851
34. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature, 1996, 384: 641-643
35. Ogryzko VV, Schiltz RL, Russanova V et al. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell, 1996, 87: 953-95936. Chen JD, Evans RM. Atransctitional co-repressor that interacts with nuclear hormone receptors. Nature, 1995, 377: 454-456
37. Spencer TE, Jenster G, Burcin MM et al. Steroid receptor coactivator one is a histone acetyltransferase. Nature, 1997, 389: 194-198
38. Yang XJ, Ogryzko VV, Nishikawa J et al. A p300 CBP-associated factor that competes with the adenoviral oncoprotein EIA. Nature, 1996, 382: 319- 324
39. Jenster G, Spencer TE, Burcin MM et al. Steroid receptor induction of gene transcription: A two-step model. Proc Natl Acad Sci USA, 1997, 94: 7879- 7884
40. Fryer CJ, Archer TK. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature, 1998, 393: 88-91
41. Chiba H, Muramatsu M, Nomoto A et al. Two human homologues of Saccharomyces cerevisiae SW12/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res, 1994,22: 1815-1820
42. Ichinose H, Garnier JM, Chambon P et al. Ligand-dependent interaction between the estrogen receptor and the human homologues of SW12/SNF2. Gene, 1997,188:95-100
43. Dallas PB, Cheney IW, Liao DW et al. P300/CREB binding protein- related protein p270 is a component of mammalian SWI/SNF complexes. Mol Cell Biol, 1998, 18:3596-3603
44. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding gy acetylation of the p53 C-terminal domain. Cell, 1997, 90: 595-606
45. Imhof A, Yang XJ, Ogryzko VV et al. Acetylation of general transcription factors by histone acetyltransferases. Curr Biol, 1997, 7:689-69246. Shim WS, DiRenzo J, DeCaprio JA et al. Proc Natl Acad Sci USA, 1999, 96: 208-213
47. Puigserver P, Wu Z, Park CW et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92: 829-839
48. Lanz RB, McKenna N J, Onate SA et al. Cell, 1999, 97: 17-27
49. Zwijsen RM, Buckle RS, Hijmans EM et al. Genes Dev, 1998, 12: 3488-3498
50. Hammer GD, Krylova I, Zhang Y et al. Mol Cell, 1999.
51. Hu E, Kim JB, Sarraf Pet al. Science, 1996, 274, 2100-2103
52. Shao D, Rangwala SM, Bailey ST et al. Nature, 1998, 396: 377-380
53. Rachez C, Suldan Z, Ward J et al. Cenes Dev, 1998, 12: 1787-1800
54. Fondell JD, Ge H, Roeder RG. Proc Natl Acad Sci USA, 1996, 93: 8329-8333
55. Gu W, Malik S, Ito M et al. Mol Cell, 1999, 3: 97-108
56. Smith DF, Toft DO. Steroid receptors and their associate proteins. Mol Endocrinol, 1993, 7: 4-11
57. Chen H, Lin RJ, Schiltz RL et al. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 1997, 90: 569-580
58. Horlein AJ, Naar AM, Heinzel T et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature, 1995, 377: 397-403
59. Sande S, Privalsky ML. Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. Mol Endocrinol, 1996, 10: 813-825
60. Seol W, Mahon M J, Lee YK et al. Two receptor interacting domains in??the nuclear hormone recepot corepressor RIP13/N-Cor. Mol Endocrinol, 1996, 10: 1646-1655
61. Baniahmad A, Kohne AC, Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor in the v-erbA oncogene product and in the retinoic acid receptor. EMBO J, 1992, 11: 1015-1023
62. Casanova J, Helmer E, Selmi-Ruby S et al. Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor. Mol Cell Biol, 1994, 14: 5756-5765
63. Baniahmad A, Leng X, Burris TP et al. The t4 activation domain of the thyroid hormone receptor is required for release of a putative corepressors necessary for transcriptional silencing. Mol Cell Biol, 1995, 15: 76-86
64. Allad L, Muhle R, Hou H et al. Role for N-CoR and histone deacetylase in Sin3-mediate transcriptional repression. Nature, 1997, 387: 49-55
65. Heinzel T, Lavinsky RM, Mullen TM et al. A complex containing N- CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997,387:43-48
66. Nagy L, Kao HY, Chakravarti D et al. Nuclear receptor repression mediated by a comples containing SMRT, mSin3A and histone deacetylase. Cell, 1997,89:373-380
67. Wong J, Patterton D, ImhoffA et al. Distinct requirements for chromatin assenbly in transcriptional repression by thyroid hormone receptor and histone deacetylase. EMBO J, 1998, 17: 520-534
68. Bartsch J, Truss M, Bode J et al. Moderate increase in histone acetylation activates the mouse mammary tumor virus promater and remodels its necleosome structure. Proc Natl Acad Sci USA, 1996, 93: 10741-10746
69. Garcia-Villalba P, Jimenez-Lara AM, Castillo Al et al. Histone??acetylation influences thyroidhormone and retinoic acid-mediated gene expression. DNA Cell Biol, 1997, 16: 421-431
70. Minucci S, Horn V, Bhattacharyya N, Russanova V et al. A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells. Proc Natl Acad Sci USA, 1997, 94: 11295-11300
71. Vegeto E, Allan GF, Schrader WT et al. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell, 1992, 69(4): 703-713
72. Xu J, Nawaz Z, Tsai SY et al. The extreme C terminus of progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor. Proc Natl Acad Sci USA, 1996, 93: 12196-12199
73. Jackson TW, Richer JK, Bain DL et al. The partial agonist activity of antagonist -occupied steroid receptors is controlled by a novel hinge domain- binding coactivator L7/SPA and the corepressors N-CoR or SMRT. Mol Endocrinol, 1997, 11:693-705
74. Wagner BL, Norris JD, Knotts TA et al. The nuclear corepressors NcoR and SMRT are key regulators of both ligand- and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Mol Cell Biol, 1998, 18: 1369-1378
75. Zhang X, Jeyakumar M, Petukhov S et al. A nuclear receptor corepressor modulates transcriptional activity of antagonist-occupied steroid hormone receptor. Mol Endocrinol, 1998,12: 513-524
76. Smith CL, Nawaz Z, O'Malley BW et al. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4- hydroxytamoxifen. Mol Endocrinol, 1997, 11: 657-666
77. Lavinsky RM, Jepsen K, Heinzel T et al. Diverse signaling pathways??modulate nuclear receptor recruitment of N-CoR and SMRT conplexes. Proc Natl Acad Sci USA, 1998, 95: 2920-2925
78. Osborne CK, Fuqua SA. Mechanisms of tamoxifen resistance. Breast Cancer Res Treat, 1994, 32: 49-55
79. Xu J, Qiu Y, DeMayo FJ et al. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science, 1998, 279: 1922-1925
80. Yao TP, Oh SP, Fuchs M et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell, 1998, 93: 361-372
81. Petrij F, Giles RH, Dauwerse HG et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional coactivator CBP. Nature, 1995, 376: 348-351
82. Anzick SL, Kononen J, Walker RL et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science, 1997, 277: 965-968
王艳林，沈珝诽，梅树恩，莫显明，刘巨洪，吴宁华．1996，科学通报，18：1699-1702
Bernd S and Ulrich G. 1997, The function of steroid horone receptors is inhibited by the hsp90-specific compound geldanamycin. J. Biol. Chem., 272:18694-18701
Bohen SP and Yamamoto KR. 1993, Isolation of Hsp90 mutants by screening for decreased steroid receptor function. Proc. Natl. Acad. Sci. USA, 90:11424-11428
Bresnick EK, Dalman FC, Sanchez ER and Pratt WB. 1989, Evidence that the 90-kDa heat shock protein is necessary for the steroid binding conformation of the L cell glucocorticoid receptor. J. Biol. Chem., 264:4992-4997
Brugge JS, Erikson E and Erikson RL. 1981, The specific interaction of the Rous Sarcoma virus transforming protein pp60src, with two cellular proteins. Cell, 25: 363-372
Bugge TH, Pohl J, Lonnoy O and Stunnenberg HG. 1992, RXRα, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J, 11:1409-1418
Casteels K, Bouillon R, Waer M and Mathieu C. 1995, Immunomodulatory effects of VD3. Curr. Opin. Nephrol. Hypertens., 4:313-318
Chen CF, Chen Y, Dai K, Chen PL, Riley DJ and Lee WH. 1996, A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. Mol. Cell. Biol., 16:4691-4699
Chen JD and Evans RM. 1995, A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature, 377:454-457
Craig TA, Lutz WH and Kumar R. 1999, Association of prokaryotic and eukaryotic chaperone proteins with the human 1α,25-dihydroxyvitamin D3 recepor. Biochem. Biophy. Res. Commun., 260:446-452Dai K, Kobayashi R and Beach D. 1996, Physical interaction of mammalian CDC37 with CDK4. J. Biol. Chem., 271: 22030-22034
Dalman FC, Ronald JK, Perdew GH, Massa E and Pratt WB. 1990, In contrast to the glucocorticoid receptor, the thyroid hormone receptor is translated in the DNA binding state and is not associated with hsp90. J. Biol. Chem., 265: 3615-3618
Dalman FC, Sturzenbecker LJ, Levin aa, Lucas DA, Perdew GH, Petkovitch M, Chambon P, Grippo JF and Pratt WB. 1990, Retinoid acid receptor belongs to a subclass of nuclear receptors that do not form "docking" complexes with hsp90. Biochemistry, 30: 5605-5608
Edmondson DG, Roth SY. 1996, Chromatin and transcription. FASEB J, 10: 1173- 1182
Forman BM, Umesono K, Chen J and Evans RM. 1995, Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell, 81: 541-550
Freedman LP. 1999, Increasing the complexity of coactivation in nuclear receptor signaling. Cell, 97:5-10
Hartl FU. 1996, Molecular chaperones in cellular protein folding. Nature, 381: 571- 580
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, Dominguez CE and Jurutka PW. 1998, The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J. Bone Mineral Res., 13:325-349
Heads RJ, Yellon DM and Latchman DS. 1995, Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells. J. Mol. Cell. Cardiol., 27: 1669-1678
Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L. 1996, Nuclear receptor coactivators and corepressors. Mol Endocrinol, 10: 1167-1177Hunter T and Poon RYC. 1997, Cdc37: a protein kinase chaperone? Trends Cell Biol.,7: 157-161
Jakob U, Lilie H, Meyer I and Buchner J. 1995, Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo. J. Biol. Chem., 270: 7288-7294
June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF and Samuelson LE. 1990, Inhibition of tyrosine phosphorylation prevents T-cell receptor- mediated signal transduction. Proc. Natl. Acad. Sci. USA, 87: 7722-7726
Kang KI, Devin J, Cadepond F, Jibard N, Guiochon-Mantel A, Baulieu EE and Catelli MG. 1994, In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus. Proc. Natl. Acad. Sci. USA, 91: 340-344
Kavva S, Nikaido T, Aoki Y, Zhai Y, Kumagai T, Furihata K, Fujii S, Kiyosawa K. 1997, Vitamin D analogues up-regulate p21 and p27 during growht inhibition of pancreatic cancer cell lines. Br. J. Cancer, 76: 884-889
Kliewer SA, Umesono K, Mangelsdorf DJ and Evans RM. 1992 (a), Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D_3 signalling. Nature, 355: 446-449
Kliewer SA, Umesono K, Noonan DJ, Heyman RA and Evans RM. 1992 (b), Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature, 358: 771-774
Kurokawa R, DiRenzo J, Boehm M, Sugarman J, Gloss B, Rosenfeld MG, Heyman RA and Glass CK. 1994, Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature, 371, 528-531
Luisi BF, Xu W, Otwinowski Z, Freedman LP, Yamamoto KR and Sigler PB. 1991, Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA .??Natrue (London) 352: 497-505
Marks MS, Hallenbeck PL, Nagata T, Segars JH, Appella E, Nikodem VM and Ozato K. 1992, H-2RIIBP (RXRp) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J, 11: 1419-1435
Mayer MP and Bernd Bukau. 1999, Current Biol., 9: R322-R325
Mendel DB and Orti E. 1988, Isoform composition and stoichiometry of the 90 kDaheat shock protein associated with glucocorticoid receptors J. Biol. Chem., 263: 6695-6702
Miyata U and Yahara I. 1995, Interaction between casein kinase II and the 90-kDa stress protein, Hsp90. Biochemistry, 34: 8123-8129
Naar AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK and Rosenfeld MG. 1991, The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell, 65: 1267-1279
Nair SC, Toran EJ, Rimerman RA et al. 1996, A pathway of multi-chaperon interactions common to diverse regulatory proteins-estrogen receptor, fes tyrosine kinase, heat shock trascription factor, HSF1, and the aryl hydrocarbon receptor. Cell Stress Chaperones, 1: 237-250
Nathan DF, Vos MH and Lindquist S. In vivo functions of the Saccharomyces cerevisiae hsp90 chaperone. Proc. Natl. Acad. Sci. USA, 94: 12949-12956
Naveilhan P, Nevey I, Wion D and Brachet P. 1996, 1,25-dihydroxyvitamin D3, and inducer of glial cell line-derived neurotrophic factor. Neuroreport, 7:2171-2175
O'Connell TD, Simpson RU. 1995, 1,25-dihydroxyvitamin D3 regulation of myocardial growth and c-myc levels in the rat heart. Biochem Biophys Res Commun, 213: 59-65
Perlmann T and Evans RM. 1997, Nuclear receptors in Sicily: All in the famiglia.??Cell, 90: 391-397
Pratt WB. 1997, The role of the hsp90-based chaperone system in signal transduction by nuclear receptor and receptors signaling via MAP kinase. Annu. Rev. Pharmacol. Toxicol., 37: 297-326
Pratt WB and Toft DO. 1997, Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr. Rev., 18: 306-360
Rutherford SL, Lindquist S: Hsp90 as a capacitor for morphological evolution. Nature, 396: 336-342
Sambrook J, et al. 1989, Molecular cloning, A laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press.
Selden, RF. Transfection using DEAE-Dextran. In: Ausubel, FM, Brent R, Kinston RE, eds. Current protocol in molecular biology, 3rd ed. New York: John Wiley & Sons Inc., 1987.9-9-9-11
Sepehrnia B, Paz IB, Dasgupta G and Momand J. 1996, Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell. J. Biol. Chem., 271: 15084-15090
Shen YF, Liu JH, Wang XZ, Wu NH. 1997, Essential roles of first intron in transcription regulation of hsp90β gene. FEBS letters, 413: 92-96
Shen YF and Wen GY. 1999, Adv. Med. Mol. Biol., 2: 205-208
Simboli-Campbell M, Narvaez CJ, van Weelden K, Tennis-wood M and Welsh J. 1997, Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells. Cancer Res Treat, 42: 31-41
Smith DF and Toft DO. 1993, Steroid recptors and their associated proteins. Mol. Endocrinol., 7: 4-11
Stancato LF, Chow YH, Hutchison KA, Perdew GH, Jove R and Pratt WB. 1993, Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a??cell-free system. J. Biol. Chem., 268: 21711-21716
Stancato LF, Silverstein AM, Owens-Grillo JK, Chow YH, Jove R and Pratt WB. 1997, The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of Raf kinase. J. Biol. Chem., 272: 4013-4020
Stepanova L, Leng XH, Parker SB and Harper JW. 1996, Mammalian p50~(cdc37) is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev., 10: 1491-1502
Trent JD, Kagawa HK, Yaoi T, Olle E and Zaluzec NJ. 1997, Chaperonin filaments: the archaeal cytoskeleton? Prox Natl. Acad Sci. USA, 94: 5383-5388
Uehara Y, Murakami Y, Mizuno S and Kawai. 1988, Inhibition of transforming activity of tyrosine kinase oncogenes by herbimycin A. Virology, 164: 294-298
Umesono K, Murakami KK, Thompson CC and Evans RM. 1991, Direct repeats as selective response elements for the thyroid hormone, retioic acid and vitamin D3 receptors. Cell, 65: 1255-1266
Whitesell L, Mimnaugh EG, De Costa B, Myers CE and Neckers LM. 1994, Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA, 91: 8324-8328
Xiao L, Lang WH. A dominant role for the c-jun NH2-terminal kinase in oncogenic Ras-induced morphologic transformation of human lung carcinoma cells. Cancer Res, 2000, 60: 400-408
Yahara I, Iida H and Koyasu S. 1986, A heat shock-resistant variant of Chinese hamster cell line constitutively expressing heat shock protein of Mr 90,000 at high level. Cell Struct. Funct., 11: 65-73Yonehara M, Minami Y, Kawata Y, Nagai J and Yagara I. 1996, Heat-induced chaperone activity of HSP90. J. Biol. Chem., 271: 2641-2645
Yu VC, Delsert C, Andersen B, Holloway M, Naar AM, Kim SY, Boutin JM, Glass CK and Rosenfeld M. 1991, RXRβ: a coregulator that enhances binding of retinoic acid, thyroid hormone and vitamin D receptors to their cognate response elements. Cell, 67: 1251-1266
Zhang XK, Hoffmann B, Tran PBV, Graupner G and M Pfahl 1992, Retinoid X receptor is an auxiliary protein for thyroid hormones and retioic acid receptors. Nature (London), 355: 441-4461. Tsai MJ et al. Annu Rev Biochem, 1994, 63:451-86
2. Lemon BD, Freedman LP. Nuclear receptor cofactors as chromatin remodelers. Curr Opin Genet Dev, 1999, 9:499-504
3. Leid M, Kastner P, Chambon P. Trends Biochem Sci, 1992,17:427-433
4. Chambon P. FASEB J, 1996,10:940-954
5. Nagpal S, Saunders M, Kastner Pet al. Cell, 1992, 70:1007-1019
6. Nagpal S, Friant A, Chambon P et al. EMBO J, 1993, 12:2349-2360
7. Glass CK, Rose DW, Rosenfeld MG. Nuclear receptor coactivators. Curr Opin Cell Biol, 1997, 9:222-232
8. Moras D, Gronemeyer H. Curr Opin Cell Biol, 1998, 10:384-391
9. Mangelsdorf DJ et al. Cell, 1995, 83:835-839
10. Cooney AJ et al. Biochem Biophys Res Commun, 1998, 245 (1): 94-100
11. Pratt WB. Annu Rev Pharmacol Toxicol, 1997, 37:297-326
12. Freedman LP. Increasing the complexity of coactivation in nuclear receptor signaling. Cell, 1999,97:5-8
13. Adams CC, Workman JL. Nucleosome displacement in transcription. Cell, 1993, 72:305-308
14. Beato M, Sanchez-Pacheco A. Interaction of steroid hormone receptors with the transcription initiation complex. Endocr Rev, 1996, 17:587-609
15. Schwerk C, Klozbucher M, Sachs M, Ulber Vet al. Identification of a??transactivation function in the progesterone receptor that interacts with the TAFII 110 subunit of the TFIID complex. J Biol Chem, 1995,270: 21331-21338
16. Ford J, McEwan IJ, Wright APH et al. Involvement of the transcription factor IID protein complex in gene activation by the N-terminal transactivation domain of the glucocorticoid receptor in vitro. Mol Endocrinol, 1997, 11: 1467- 1475
17. McEwan IJ, Gustofsson JA. Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF. Proc Natl Acad Sci USA, 1997, 94:8485-8490
18. Tasset D, Tora L, Fromental C et al. Distinct classes of transcriptional activating domains function by different mechanisms. Cell, 1990, 62: 1177-1187
19. Horwitz KB, Jackson TA, Bain DL et al. Nuclear receptor coactivators and corepressors. Mol Endocrinol, 1996, 10: 1167-1177
20. Shibata H, Spencer TE, Onate SA et al. Role of coactivators and corepressors in the mechanism of steroid thyroid receptor action. Recent Prog Horm Res, 1997,52:1-25
21. L'Horset F, Dauvois S, Heery DM et al. RIP-140 interacts with multiple nuclear receptors by means of two distinct sites. Mol Cell Biol, 1996, 11: 6029- 6036
22. Ding XF, Anderson CM, Ma H et al. Nuclear receptor-binding sites of coactivators glucocorticokd receptor interacting protein I (GRIP1) and steroid receptor coactivator 1 (SRC-1): Mutiple motifs with different binding specificities. Mol Endocrinol, 1998, 12:302-313
23. Onate SA, Boonyaratanakornkit V, Spencer TE et al. The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AFl)and AF2??domains of steroid receptors. J Biol Chem, 1998, 273: 12101-12108
24. Voegel JJ, Heine MJS, Tini M et al. The coactivator TIF2 contains three nuclear receptor -binding motifs and mediates transactivation through CBP binding-depengdent and-independent pathways. EMBO J, 1998, 17:507-519
25. Xu L, Glass CK, Rosenfeld MG. Curr Opin Genet Dev, 1999,9:140-147
26. Shiau AK, Barstad D, Loria PM et al. Cell, 1998, 95: 927-937
27. Yeh S, Chang C. Cloning and characterization of a specific coactivator ARA70 for the androgen receptor in human prostate cells. Proc Natl Acad Sci USA, 1996,93:5517-5521
28. Swanson HL, Bradfield CA. The AH-receptor: Genetics structure and function. Pharmacogenetics, 1993, 3:213-230
29. Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol, 1995, 35: 307-340
30. Tsukiyama T, Wu C. Chromatin remodeling and transcription. Genes Dev, 1997, 7: 182-191
31. Getzenberg RH, Pienta KJ, Ward WS et al. Nuclear structure and the three-dimensional organization of DNA. J Cell Biochem, 1991,47: 289-299
32. Wolffe AP, Pruss D. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell, 1996, 86: 817-819
33. Brownell JE, Zhou J, Ranalli T et al. Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell, 1996, 84, 943-851
34. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature, 1996, 384: 641-643
35. Ogryzko VV, Schiltz RL, Russanova V et al. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell, 1996, 87: 953-95936. Chen JD, Evans RM. Atransctitional co-repressor that interacts with nuclear hormone receptors. Nature, 1995, 377: 454-456
37. Spencer TE, Jenster G, Burcin MM et al. Steroid receptor coactivator one is a histone acetyltransferase. Nature, 1997, 389: 194-198
38. Yang XJ, Ogryzko VV, Nishikawa J et al. A p300 CBP-associated factor that competes with the adenoviral oncoprotein EIA. Nature, 1996, 382: 319- 324
39. Jenster G, Spencer TE, Burcin MM et al. Steroid receptor induction of gene transcription: A two-step model. Proc Natl Acad Sci USA, 1997, 94: 7879- 7884
40. Fryer CJ, Archer TK. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature, 1998, 393: 88-91
41. Chiba H, Muramatsu M, Nomoto A et al. Two human homologues of Saccharomyces cerevisiae SW12/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res, 1994,22: 1815-1820
42. Ichinose H, Garnier JM, Chambon P et al. Ligand-dependent interaction between the estrogen receptor and the human homologues of SW12/SNF2. Gene, 1997,188:95-100
43. Dallas PB, Cheney IW, Liao DW et al. P300/CREB binding protein- related protein p270 is a component of mammalian SWI/SNF complexes. Mol Cell Biol, 1998, 18:3596-3603
44. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding gy acetylation of the p53 C-terminal domain. Cell, 1997, 90: 595-606
45. Imhof A, Yang XJ, Ogryzko VV et al. Acetylation of general transcription factors by histone acetyltransferases. Curr Biol, 1997, 7:689-69246. Shim WS, DiRenzo J, DeCaprio JA et al. Proc Natl Acad Sci USA, 1999, 96: 208-213
47. Puigserver P, Wu Z, Park CW et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92: 829-839
48. Lanz RB, McKenna N J, Onate SA et al. Cell, 1999, 97: 17-27
49. Zwijsen RM, Buckle RS, Hijmans EM et al. Genes Dev, 1998, 12: 3488-3498
50. Hammer GD, Krylova I, Zhang Y et al. Mol Cell, 1999.
51. Hu E, Kim JB, Sarraf Pet al. Science, 1996, 274, 2100-2103
52. Shao D, Rangwala SM, Bailey ST et al. Nature, 1998, 396: 377-380
53. Rachez C, Suldan Z, Ward J et al. Cenes Dev, 1998, 12: 1787-1800
54. Fondell JD, Ge H, Roeder RG. Proc Natl Acad Sci USA, 1996, 93: 8329-8333
55. Gu W, Malik S, Ito M et al. Mol Cell, 1999, 3: 97-108
56. Smith DF, Toft DO. Steroid receptors and their associate proteins. Mol Endocrinol, 1993, 7: 4-11
57. Chen H, Lin RJ, Schiltz RL et al. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 1997, 90: 569-580
58. Horlein AJ, Naar AM, Heinzel T et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature, 1995, 377: 397-403
59. Sande S, Privalsky ML. Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. Mol Endocrinol, 1996, 10: 813-825
60. Seol W, Mahon M J, Lee YK et al. Two receptor interacting domains in??the nuclear hormone recepot corepressor RIP13/N-Cor. Mol Endocrinol, 1996, 10: 1646-1655
61. Baniahmad A, Kohne AC, Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor in the v-erbA oncogene product and in the retinoic acid receptor. EMBO J, 1992, 11: 1015-1023
62. Casanova J, Helmer E, Selmi-Ruby S et al. Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor. Mol Cell Biol, 1994, 14: 5756-5765
63. Baniahmad A, Leng X, Burris TP et al. The t4 activation domain of the thyroid hormone receptor is required for release of a putative corepressors necessary for transcriptional silencing. Mol Cell Biol, 1995, 15: 76-86
64. Allad L, Muhle R, Hou H et al. Role for N-CoR and histone deacetylase in Sin3-mediate transcriptional repression. Nature, 1997, 387: 49-55
65. Heinzel T, Lavinsky RM, Mullen TM et al. A complex containing N- CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997,387:43-48
66. Nagy L, Kao HY, Chakravarti D et al. Nuclear receptor repression mediated by a comples containing SMRT, mSin3A and histone deacetylase. Cell, 1997,89:373-380
67. Wong J, Patterton D, ImhoffA et al. Distinct requirements for chromatin assenbly in transcriptional repression by thyroid hormone receptor and histone deacetylase. EMBO J, 1998, 17: 520-534
68. Bartsch J, Truss M, Bode J et al. Moderate increase in histone acetylation activates the mouse mammary tumor virus promater and remodels its necleosome structure. Proc Natl Acad Sci USA, 1996, 93: 10741-10746
69. Garcia-Villalba P, Jimenez-Lara AM, Castillo Al et al. Histone??acetylation influences thyroidhormone and retinoic acid-mediated gene expression. DNA Cell Biol, 1997, 16: 421-431
70. Minucci S, Horn V, Bhattacharyya N, Russanova V et al. A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells. Proc Natl Acad Sci USA, 1997, 94: 11295-11300
71. Vegeto E, Allan GF, Schrader WT et al. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell, 1992, 69(4): 703-713
72. Xu J, Nawaz Z, Tsai SY et al. The extreme C terminus of progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor. Proc Natl Acad Sci USA, 1996, 93: 12196-12199
73. Jackson TW, Richer JK, Bain DL et al. The partial agonist activity of antagonist -occupied steroid receptors is controlled by a novel hinge domain- binding coactivator L7/SPA and the corepressors N-CoR or SMRT. Mol Endocrinol, 1997, 11:693-705
74. Wagner BL, Norris JD, Knotts TA et al. The nuclear corepressors NcoR and SMRT are key regulators of both ligand- and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Mol Cell Biol, 1998, 18: 1369-1378
75. Zhang X, Jeyakumar M, Petukhov S et al. A nuclear receptor corepressor modulates transcriptional activity of antagonist-occupied steroid hormone receptor. Mol Endocrinol, 1998,12: 513-524
76. Smith CL, Nawaz Z, O'Malley BW et al. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4- hydroxytamoxifen. Mol Endocrinol, 1997, 11: 657-666
77. Lavinsky RM, Jepsen K, Heinzel T et al. Diverse signaling pathways??modulate nuclear receptor recruitment of N-CoR and SMRT conplexes. Proc Natl Acad Sci USA, 1998, 95: 2920-2925
78. Osborne CK, Fuqua SA. Mechanisms of tamoxifen resistance. Breast Cancer Res Treat, 1994, 32: 49-55
79. Xu J, Qiu Y, DeMayo FJ et al. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science, 1998, 279: 1922-1925
80. Yao TP, Oh SP, Fuchs M et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell, 1998, 93: 361-372
81. Petrij F, Giles RH, Dauwerse HG et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional coactivator CBP. Nature, 1995, 376: 348-351
82. Anzick SL, Kononen J, Walker RL et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science, 1997, 277: 965-968