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:

RBP1 induces growth arrest by repression of E2F-dependent transcription

Abstract

Growth arrest and cell cycle progression are regulated by the retinoblastoma tumour suppressor pRB and related proteins p130 and p107 that bind to and inhibit the E2F family of transcription factors. Although the precise mechanism of this inhibition remains to be established, previous studies indicated the presence of transcriptional repression activity in the `pocket' of RB family members. We show here that RBP1, a known pRB pocket-binding protein, possesses transcriptional repression activity and associates with p130-E2F and pRB-E2F complexes specifically during growth arrest. Overexpression of RBP1 both inhibited E2F-dependent gene expression and suppressed cell growth. Thus repression of E2F-dependent transcription by RBP1 via RB family members may play a central role in inducing growth arrest.

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

Similar content being viewed by others

References

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

  • Buchkovich K, Duffy LA and Harlow E. . 1989 Cell 58: 1097–1105.

  • Buyse IM, Shao G and Huang S. . 1995 Proc. Natl. Acad. Sci. USA 92: 4467–4471.

  • Cao L, Faha B, Dembski M, Tsai LH, Harlow E and Dyson N. . 1992 Nature 355: 176–179.

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

  • Chen P-L, Scully P, Shew J-Y, Wang JYJ and Lee W-H. . 1989 Cell 58: 1193–1198.

  • Chittenden T, Livingston DM and DeCaprio JA. . 1993 Mol. Cell. Biol. 13: 3975–3983.

  • Chow KNB and Dean DC. . 1996 Mol. Cell Biol. 16: 4862–4868.

  • Chow KNB, Starostik P and Dean DC. . 1996 Mol. Cell. Biol. 16: 7173–7181.

  • Cobrinik D, Whyte P, Peeper DS, Jacks T and Weinberg RA. . 1993 Genes Dev. 7: 2392–2404.

  • Corbeil HB, Whyte P and Branton PE. . 1995 Oncogene 11: 909–920.

  • Corbeil HB and Branton PE. . 1997 Oncogene 15: 657–668.

  • Coté J, Quinn J, Workman JL and Peterson CL. . 1994 Science 265: 53–60.

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang C-M and Livingston DM. . 1989 Cell 58: 1085–1095.

  • Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE and Oliff A. . 1991 Nature 353: 251–254.

  • Dunalef JL, Strober BE, Guha S, Khavari PA, Ã…lin K, Luban J, Begemann M, Crabtree GR and Goff SP. . 1994 Cell 79: 119–130.

  • Fattaey AR, Helin K, Dembski MS, Dyson N, Harlow E, Vuocolo GA, Hanobik MG, Haskell KM, Oliff A, Defeo-Jones D and Jones R. . 1993 Oncogene 8: 3149–3156.

  • Graham FL, Smiley J, Russell WC and Nairn R. . 1977 J. Gen. Virol. 36: 59–72.

  • Graham FL and van der Eb AJ. . 1973 Virology 52: 456–467.

  • Gregory SL, Kortschak RD, Kajionis B and Saint R. . 1996 Mol. Cell. Biol., 16: 792–799.

  • Herrscher RF, Kaplan MH, Lelsz DL, Das C, Sheuermann R and Tucker PW. . 1995 Genes Dev. 9: 3067–3082.

  • Hsiao K-M, McMahon SL and Farnham PJ. . 1994 Genes Dev. 8: 1526–1537.

  • Huang TH, Oka T, Asai T, Okada T, Merrills BW, Gertson PN, Whitson RH and Itakura K. . 1996 Nucl. Acids Res. 24: 1695–1701.

  • Johnson DG, Schwarz JK, Cress WD and Nevins JR. . 1993 Nature 365: 349–352.

  • Johnson DG, Ohtani K and Nevins JR. . 1994 Genes Dev. 8: 1514–1525.

  • Johnson DG. . 1995 Oncogene 11: 1685–1692.

  • Kaelin WJ, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA, Livingston DM and Flemington EK. . 1992 Cell 70: 351–364.

  • Kim YW, Otterson GA, Kratzke RA, Coxon AB and Kaye FJ. . 1994 Mol. Cell Biol. 14: 7256–7264.

  • La Thangue NB. . 1994 Cur. Opin. Cell. Biol. 6: 443–450.

  • Lees E, Faha B, Dulic V, Reed SI and Harlow E. . 1992 Genes Dev. 6: 1874–1885.

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

  • 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.

  • Mihara K, Cao X-R., Yen A, Chandler S, Driscoll B, Murphree AL, Tang A and Fung Y-KT. . 1989 Science 246: 1300–1303.

  • Mitsudomi T, Steinberg SM., Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD and Gazdar AF. . 1992 Oncogene 7: 171–180.

  • Nevins JR. . 1992 Nature 358: 375–376.

  • Otterson GA, Kratzke RA, Lin AY, Johnston PG and Kaye FJ. . 1993 Oncogene 8: 949–957.

  • Pöpperl H and Featherstone MS. . 1992 EMBO J. 11: 3673–3680.

  • Shirodkar S, Ewen M, DeCaprio JA, Morgon J, Livingston DM and Chittenden T. . 1992 Cell 68: 157–166.

  • Smith EJ, Leone G, DeGregori J, Jakoi I and Nevins JR. . 1996 Mol. Cell. Biol. 16: 6965–6976.

  • Starostik P, Chow KNB and Dean DC. . 1996 Mol. Cell. Biol. 16: 3606–3614.

  • Strober BE, Dunaief JL, Guha S and Goff SP. . 1996 Mol. Cell. Biol. 16: 1576–1583.

  • Teodoro JG, Halliday T, Whalen SG, Takayesu D, Graham FL and Branton PE. . 1994 J. Virol. 68: 776–786.

  • Teodoro JG and Branton PE. . 1997 J. Virol. 71: 3620–3627.

  • Tevosian SG, Shih HH, Mendelson KG, Sheppard K-A, Paulson KE and Yee AS. . 1997 Genes Dev. 11: 383–396.

  • Weintraub SJ and Dean DC. . 1992 Mol. Cell. Biol. 12: 512–517.

  • Weintraub SJ, Prater CA and Dean DC. . 1992 Nature 358: 259–261.

  • Weintraub SJ, Chow KNB, Luo RX, Zhang SH, He S and Dean DC. . 1995 Nature 375: 812–815.

  • Wrana JL, Attisano L, Cárcamo J, Zentella A, Doody J, Laiho M, Wang W-F and Massagué J. . 1992 Cell 71: 1003–1014.

  • Yew PR, Liu X and Berk AJ. . 1994 Genes Dev. 8: 190–202.

Download references

Acknowledgements

We wish to thank the following colleagues for their generous contributions: Jim DeCaprio for anti-RBP1 serum LY11, Bill Kaelin for the RBP1 and pRB cDNAs, Joe Nevins and David Johnson for E2F1-Luc(Wt) and E2F1-Luc(mE2F), Ed Harlow for the p107 cDNA, Peter Whyte for the p130 cDNA and 896 antibodies, and Arnie Berk for pSG424 and G5TKCAT. This work was supported by grants from the National Cancer Institute of Canada and the Medical Research Council of Canada. HBC had a Studentship from the MRC.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lai, A., Marcellus, R., Corbeil, H. et al. RBP1 induces growth arrest by repression of E2F-dependent transcription. Oncogene 18, 2091–2100 (1999). https://doi.org/10.1038/sj.onc.1202520

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202520

Keywords

This article is cited by

Search

Quick links