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:

CBP/p300 histone acetyl-transferase activity is important for the G1/S transition

Abstract

Transforming viral proteins such as E1A which force quiescent cells into S phase have two essential cellular target proteins, Rb and CBP/p300. Rb regulates the G1/S transition by controlling the transcription factor E2F. CBP/p300 is a transcriptional co-activator with intrinsic histone acetyl-transferase activity. This activity is regulated in a cell cycle dependent manner and shows a peak at the G1/S transition, suggesting a function for CBP/p300 in this crucial step of the cell cycle. Here, we have artificially modulated CBP/p300 levels in individual cells through microinjection of specific antibodies and expression vectors. We show that CBP/p300 is required for cell proliferation and has an essential function during the G1/S transition. Using the same microinjection system and GFP-reporter vectors, we demonstrate that CBP/p300 is essential for the activity of E2F, a transcription factor that controls the G1/S transition. In addition, our results suggest that CBP HAT activity is required both for the G1/S transition and for E2F activity. Thus CBP/p300 seems to be a versatile protein involved in opposing cellular processes, which raises the question of how its multiple activities are regulated.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

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 and Harel-Bellan A . 1998a Nature 396: 184–186

  • Ait-Si-Ali S, Ramirez S, Robin P, Trouche D and Harel-Bellan A . 1998b Nucl Acid Res 26: 3869–3870

  • Arany Z, Newsome D, Oldread E, Livingston DM and Eckner R . 1995 Nature 374: 81–84

  • Bannister AJ and Kouzarides T . 1996 Nature 384: 641–643

  • Bennett JD, Farlie PG and Watson RJ . 1996 Oncogene 13: 1073–1082

  • Bernards R . 1997 Biochem Biophys Acta 1333: 33–40

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ and Kouzarides T . 1998 Nature 391: 597–601

  • Chakravarti D, Ogryzko V, Kao HY, Nash A, Chen H, Nakatani Y and Evans RM . 1999 Cell 96: 393–403

  • Chellappan SP, Hiebert S, Mudryj M, Horowitz JM and Nevins JR . 1991 Cell 65: 1053–1061

  • Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y and Evans RM . 1997 Cell 90: 569–580

  • Chiarugi V, Cinelli M and Magnelli L . 1998 Oncol Res 10: 55–57

  • DeGregori J, Kowalik T and Nevins JR . 1995 Mol Cell Biol 15: 4215–4224

  • Dyson N, Buchkovich K, Whyte P and Harlow E . 1989 Princess Takamatsu Symp 20: 191–198

  • Eckner R . 1996 Biol Chem 377: 685–688

  • Eckner R, Yao TP, Oldread E and Livingston DM . 1996 Genes Dev 10: 2478–2490

  • Fry CJ, Pearson A, Malinowski E, Bartley SM, Greenblatt J and Farnham PJ . 1999 J Biol Chem 274: 15883–15891

  • Giles RH, Peters DJM and Breuning MH . 1998 Trends Genet 14: 178–183

  • Goldman PS, Tran VK and Goodman RH . 1997 Recent Prog Horm Res 52: 103–119; discussion 119–120

  • Groisman R, Masutani H, Leibovitch MP, Robin P, Soudant I, Trouche D and Harel-Bellan A . 1996 J Biol Chem 271: 5258–5264

  • Gu W and Roeder RG . 1997 Cell 90: 595–606

  • Gu W, Shi XL and Roeder RG . 1997 Nature 387: 819–823

  • Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y and Kedes L . 1999 Cell 96: 405–413

  • Hasegawa K, Meyers MB and Kitsis RN . 1997 J Biol Chem 272: 20049–20054

  • Hateboer G, Wobst A, Petersen BO, Le Cam L, Vigo E, Sardet C and Helin K . 1998 Mol Cell Biol 18: 6679–6697

  • Janknecht R and Hunter T . 1996 Curr Biol 6: 951–954

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

  • Karuppayil SM, Moran E and Das GM . 1998 J Biol Chem 273: 17303–17306

  • Kee BI, Arias J and Montminy MR . 1996 J Biol Chem 271: 2373–2375

  • Kitabayashi I, Yokoyama A, Shimizu K and Ohki M . 1998 EMBO J 17: 2994–3004

  • Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK and Rosenfeld MG . 1998 Science 279: 703–707

  • Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR and Goodman RH . 1994 Nature 370: 223–226

  • Lam EW and Watson RJ . 1993 EMBO J 12: 2705–2713

  • Lee BH and Mathews MB . 1997 Proc Natl Acad Sci USA 94: 4481–4486

  • Lee CW, Sorensen TS, Shikama N and Lathangue NB . 1998 Oncogene 16: 2695–2710

  • Li Q, Imhof A, Collingwood TN, Urnov FD and Wolffe AP . 1999 EMBO J 18: 5634–5652

  • Lill NL, Grossman SR, Ginsberg D, DeCaprio J and Livingston DM . 1997 Nature 387: 823–827

  • Lundblad JR, Kwok RP, Laurance ME, Harter ML and Goodman RH . 1995 Nature 374: 85–88

  • Luo RX, Postigo AA and Dean DC . 1998 Cell 92: 463–473

  • Magnaghi-Jaulin L, Ait-Si-Ali S and Harel-Bellan A . 1999 Semin Cell Dev Biol 10: 197–203

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harel-Bellan A . 1998 Nature 391: 601–605

  • Mink S, Haenig B and Klempnauer KH . 1997 Mol Cell Biol 17: 6609–6617

  • Missero C, Calautti E, Eckner R, Chin J, Tsai LH, Livingston DM and Dotto GP . 1995 Proc Natl Acad Sci USA 92: 5451–5455

  • Muraoka M, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Shitara N, Chong JM, Iwama T and Miyaki M . 1996 Oncogene 12: 1565–1569

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

  • Nevins JR . 1998 Cell Growth Differ 9: 585–593

  • Nevins JR, Leone G, Degregori J and Jakoi L . 1997 J Cell Physiol 173: 233–236

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH and Nakatani Y . 1996 Cell 87: 953–959

  • Puri PL, Avantaggiati ML, Balsano C, Sang N, Graessmann A, Giordano A and Levrero M . 1997a EMBO J 16: 369–383

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

  • Ramirez S, Ali SAS, Robin P, Trouche D and Harel-Bellan A . 1997 J Biol Chem 272: 31016–31021

  • Sartorelli V, Huang J, Hamamori Y and Kedes L . 1997 Mol Cell Biol 17: 1010–1026

  • Satake N, Ishida Y, Otoh Y, Hinohara S, Kobayashi H, Sakashita A, Maseki N and Kaneko Y . 1997 Genes Chromosomes Cancer 20: 60–63

  • Sato S, Roberts K, Gambino G, Cook A, Kouzarides T and Goding CR . 1997 Oncogene 14: 3083–3092

  • Scolnick DM, Chehab NH, Stavridi ES, Lien MC, Caruso L, Moran E, Berger SL and Halazonetis TD . 1997 Cancer Res 57: 3693–3696

  • Shi Y and Mello C . 1998 Gene Dev 12: 943–955

  • Shikama N, Lyon J and La Thangue N . 1997 Trends Cell Biol 7: 230–236

  • Smits PH, de Wit L, van der Eb AJ and Zantema A . 1996 Oncogene 12: 1529–1535

  • Swope DL, Mueller CL and Chrivia JC . 1996 J Biol Chem 271: 28138–28145

  • Taki T, Sako M, Tsuchida M and Hayashi Y . 1997 Blood 89: 3945–3950

  • Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T and Ishii S . 1997 Proc Natl Acad Sci USA 94: 10215–10220

  • Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK and Rosenfeld MG . 1997 Nature 387: 677–684

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

  • Weinberg RA . 1992 Cancer Surv 12: 43–57

  • Wolffe AP and Pruss D . 1996 Cell 84: 817–819

  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH and Nakatani Y . 1996 Nature 382: 319–324

  • Yao TP, Oh SP, Fuchs M, Zhou ND, Chng LE, Newsome D, Bronson RT, Li E, Livingston DM and Eckner R . 1998 Cell 93: 361–372

  • Zhang HS, Postigo AA and Dean DC . 1999 Cell 97: 53–61

Download references

Acknowledgements

The authors thank Tony Kouzarides for the gift of plasmids and Linda L Pritchard for critical reading of the manuscript. This work was supported by grants from the Comité de l'Essonne and the Comité du Val de Marne de la Ligue Contre le Cancer, from the Ligue Nationale Contre le Cancer, from the Association pour la Recherche sur le Cancer, and from the European Commission (Grant QLRT-1999-00866). S Ait-Si-Ali was supported by a fellowship from the Ligue Nationale Contre le Cancer. A Polesskaya was awarded a fellowship from the FEBS organization. R Ferreira was supported by a fellowship from the Comité du Val-d'Oise de la Ligue Contre le Cancer.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ait-Si-Ali, S., Polesskaya, A., Filleur, S. et al. CBP/p300 histone acetyl-transferase activity is important for the G1/S transition. Oncogene 19, 2430–2437 (2000). https://doi.org/10.1038/sj.onc.1203562

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203562

Keywords

This article is cited by

Search

Quick links