Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Transcriptional activation by the oestrogen receptor α is modulated through inhibition of cyclin-dependent kinases

Oncogene volume 21, pages 5773–5782 (2002)Cite this article

Abstract

We have investigated the interaction between the expression of p21WAF1/CIP1/SDI1, a stoichiometric inhibitor of Cdk, and the transcriptional activity of the oestrogen receptor α (ERα). Transient transfection experiments demonstrated that the expression of p21WAF1/CIP1/SDI1 amplified the transcriptional activation by ERα. A dominant negative mutant of Cdk2 also enhanced the ERα transcriptional activity, indicating that the underlying mechanism relies on the inhibition of Cdk2 activity and cell cycle arrest. In agreement with this conclusion, experiments with p21WAF1/CIP1/SDI1 mutants demonstrated that the domain involved in the binding of p21WAF1/CIP1/SDI1 to Cdks was indispensable for the modulation of ERα activity. In addition, we show that expression of p21WAF1/CIP1/SDI1 alleviates the block on CBP function mediated by Cdk2 and in turn stimulates transcriptional activation by ERα in a CBP-histone acetyltransferase (HAT)-dependent manner. These results suggest a novel mechanism by which p21WAF1/CIP1/SDI1 functions as an enhancer of ERα activity through the modulation of CBP function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Ait-Si-Ali S, Ramirez S, Barre FX, Dkhissi F, Magnaghi-Jaulin L, Girault JA, Robin P, Knibiehler M, Pritchard LL, Ducommun B, Trouche D, Harel-Bellan A . 1998 Nature 396: 184–186

  • Altucci L, Addeo R, Cicatiello L, Dauvois S, Parker MG, Truss M, Beato M, Sica V, Bresciani F, Weisz A . 1996 Oncogene 12: 2315–2324

  • Andrews NC, Faller DV . 1991 Nucleic Acids Res. 19: 2499

  • Arias J, Alberts AS, Brindle P, Claret FX, Smeal T, Karin M, Feramisco J, Montminy M . 1994 Nature 370: 226–229

  • Beato M, Herrlich P, Schutz G . 1995 Cell 83: 851–857

  • Blanco JC, Minucci S, Lu J, Yang XJ, Walker KK, Chen H, Evans RM, Nakatani Y, Ozato K . 1998 Genes Dev. 12: 1638–1651

  • Brownell JE, Allis CD . 1995 Proc. Natl. Acad. Sci. USA 92: 6364–6368

  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ . 1995 Nature 377: 552–557

  • Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M . 1997 Nature 389: 753–758

  • Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG . 1995 EMBO J. 14: 3741–3751

  • Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M, Evans RM . 1996 Nature 383: 99–103

  • Chen H, Lin RJ, Xie W, Wilpitz D, Evans RM . 1999 Cell 98: 675–686

  • Chen J, Jackson PK, Kirschner MW, Dutta A . 1995 Nature 374: 386–388

  • Chen X, Danes C, Lowe M, Herliczek TW, Keyomarsi K . 2000 J. Natl. Cancer Inst. 92: 1403–1413

  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P . 1995 Cell 82: 675–684

  • Felzien LK, Farrell S, Betts JC, Mosavin R, Nabel GJ . 1999 Mol. Cell. Biol. 19: 4241–4246

  • Feng XH, Filvaroff EH, Derynck R . 1995 J. Biol. Chem. 270: 24237–24245

  • Font de Mora J, Brown M . 2000 Mol. Cell. Biol. 20: 5041–5047

  • Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG . 2000 J. Biol. Chem. 275: 20853–20860

  • Gagne D, Balaguer P, Demirpence E, Chabret C, Trousse F, Nicolas JC, Pons M . 1994 J. Biolumin. Chemilumin. 9: 201–209

  • Glass CK, Rosenfeld MG . 2000 Genes Dev. 14: 121–141

  • Goodman RH, Smolik S . 2000 Genes Dev. 14: 1553–1577

  • Halevy O, Novitch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ, Beach D, Lassar AB . 1995 Science 267: 1018–1021

  • Hanstein B, Eckner R, DiRenzo J, Halachmi S, Liu H, Searcy B, Kurokawa R, Brown M . 1996 Proc. Natl. Acad. Sci. USA 93: 11540–11545

  • Harper JW, Elledge SJ . 1996 Curr. Opin. Genet. Dev. 6: 56–64

  • Ing NH, Beekman JM, Tsai SY, Tsai MJ, O'Malley BW . 1992 J. Biol. Chem. 267: 17617–17623

  • Jacq X, Brou C, Lutz Y, Davidson I, Chambon P, Tora L . 1994 Cell 79: 107–117

  • Jiang H, Chou HS, Zhu L . 1998 Mol. Cell. Biol. 18: 5284–5290

  • Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG . 1996 Cell 85: 403–414

  • Kawasaki H, Eckner R, Yao TP, Taira K, Chiu R, Livingston DM, Yokoyama KK . 1998 Nature 393: 284–289

  • Klock G, Strahle U, Schutz G . 1987 Nature 329: 734–736

  • Korach KS . 1994 Science 266: 1524–1527

  • Kouzarides T . 2000 EMBO J. 19: 1176–1179

  • Kumar V, Green S, Stack G, Berry M, Jin JR, Chambon P . 1987 Cell 51: 941–951

  • Kurokawa R, Kalafus D, Ogliastro MH, Kioussi C, Xu L, Torchia J, Rosenfeld MG, Glass CK . 1998 Science 279: 700–703

  • Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP . 1996 Genes Dev. 10: 142–153

  • Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM . 1995 Cell 83: 835–839

  • McConnell BB, Gregory FJ, Stott FJ, Hara E, Peters G . 1999 Mol. Cell. Biol. 19: 1981–1989

  • McMahon C, Suthiphongchai T, DiRenzo J, Ewen ME . 1999 Proc. Natl. Acad. Sci. USA 96: 5382–5387

  • Mitra J, Dai CY, Somasundaram K, El-Deiry WS, Satyamoorthy K, Herlyn M, Enders GH . 1999 Mol. Cell. Biol. 19: 3916–3928

  • Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD, Montminy M . 1997a Cell 90: 1107–1112

  • Nakajima T, Uchida C, Anderson SF, Parvin JD, Montminy M . 1997b Genes Dev. 11: 738–747

  • Nakanishi M, Adami GR, Robetorye RS, Noda A, Venable SF, Dimitrov D, Pereira-Smith OM, Smith JR . 1995 Proc. Natl. Acad. Sci. USA 92: 4352–4356

  • Nuclear Receptors Nomenclature Committee. 1999 Cell 97: 161–163

  • Oh YL, Choi JS, Song SY, Ko YH, Han BK, Nam SJ, Yang YH . 2001 Pathol. Int. 51: 94–99

  • Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ . 1997 Science 275: 523–527

  • Planas-Silva MD, Shang Y, Donaher JL, Brown M, Weinberg RA . 2001 Cancer Res. 61: 3858–3862

  • Polesskaya A, Naguibneva I, Fritsch L, Duquet A, Ait-Si-Ali S, Robin P, Vervisch A, Pritchard LL, Cole P, Harel-Bellan A . 2001 EMBO J. 20: 6816–6825

  • Prall OW, Sarcevic B, Musgrove EA, Watts CK, Sutherland RL . 1997 J. Biol. Chem. 272: 10882–10894

  • Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y, Levrero M . 1997 Mol. Cell 1: 35–45

  • Rosenfeld MG, Glass CK . 2001 J. Biol. Chem. 276: 36865–36868

  • Rowan BG, Garrison N, Weigel NL, O'Malley BW . 2000a Mol. Cell. Biol. 20: 8720–8730

  • Rowan BG, Weigel NL, O'Malley BW . 2000b J. Biol. Chem. 275: 4475–4483

  • Sabbah M, Courilleau D, Mester J, Redeuilh G . 1999 Proc. Natl. Acad. Sci. USA 96: 11217–11222

  • Sabbah M, Kang KI, Tora L, Redeuilh G . 1998 Biochem. J. 336: 639–646

  • Sabbah M, Radanyi C, Redeuilh G, Baulieu EE . 1996 Biochem. J. 314: 205–213

  • Sartorelli V, Puri PL, Hamamori Y, Ogryzko V, Chung G, Nakatani Y, Wang JY, Kedes L . 1999 Mol. Cell 4: 725–734

  • Sherr CJ . 1994 Cell 79: 551–555

  • Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA . 1995 Cell 82: 621–630

  • Smith CL, Onate SA, Tsai MJ, O'Malley BW . 1996 Proc. Natl. Acad. Sci. USA 93: 8884–8888

  • Snowden AW, Anderson LA, Webster GA, Perkins ND . 2000 Mol. Cell. Biol. 20: 2676–2686

  • Trouche D, Cook A, Kouzarides T . 1996 Nucleic Acids Res. 24: 4139–4145

  • van den Heuvel S, Harlow E . 1993 Science 262: 2050–2054

  • Vanden Berghe W, De Bosscher K, Boone E, Plaisance S, Haegeman G . 1999 J. Biol. Chem. 274: 32091–32098

  • Waldman T, Kinzler KW, Vogelstein B . 1995 Cancer Res. 55: 5187–5190

  • Yaciuk P, Carter MC, Pipas JM, Moran E . 1991 Mol. Cell. Biol. 11: 2116–2124

  • Zhang H, Xiong Y, Beach D . 1993 Mol. Biol. Cell 4: 897–906

  • Zindy F, Lamas E, Chenivesse X, Sobczak J, Wang J, Fesquet D, Henglein B, Brechot C . 1992 Biochem. Biophys. Res. Commun. 182: 1144–1154

  • Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R . 1998 Genes Dev. 12: 3488–3498

Download references

Acknowledgements

We are very grateful to Drs B Ducommun, D Gagne, R Goodman, E Harlow, Y Nakatani, B O'Malley, R Michalides, D Trouche, L Tora and B Vogelstein for generously providing various expression vectors and cell lines. We thank D Catala for technical assistance. This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Association pour la Recherche sur le Cancer and by the Ligue Nationale contre le Cancer, Comité de Paris.

Author information

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale U 482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, Paris, Cedex 12, 75571, France

    Gérard Redeuilh, Annette Attia, Jan Mester & Michèle Sabbah

Authors
  1. Gérard Redeuilh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annette Attia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Mester
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michèle Sabbah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michèle Sabbah.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Redeuilh, G., Attia, A., Mester, J. et al. Transcriptional activation by the oestrogen receptor α is modulated through inhibition of cyclin-dependent kinases. Oncogene 21, 5773–5782 (2002). https://doi.org/10.1038/sj.onc.1205753

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205753

Keywords

This article is cited by

Search

Advanced search

Quick links