iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://doi.org/10.1038/sj.onc.1205511
Physical interaction between pRb and cdk9/cyclinT2 complex | Oncogene
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:

Physical interaction between pRb and cdk9/cyclinT2 complex

Oncogene volume 21, pages 4158–4165 (2002)Cite this article

Abstract

Cyclin-dependent kinase 9 (cdk9) is a multifunctional kinase with roles in different cellular pathways such as transcriptional elongation, differentiation and apoptosis. Cdk9/cyclin T differs functionally from other cdk/cyclin complexes that regulate cell cycle progression, but maintains structural affinity with those complexes. In addition, previous reports have demonstrated that the cdk9 complex is able to phosphorylate p56/pRb in vitro. In this report we show in vitro and in vivo interaction between cdk9/cyclinT2 and the protein product of the retinoblastoma gene (pRb) in human cell lines. The interaction involves the region composed of residues 129–195 of cdk9, cyclinT2 (1–642 aa) and the C-terminal domain of pRb (835–928 aa). We located the minimal region of cdk9 phosphorylation on the C-terminus of pRb, by identifying the residues between 793 and 834. This region contains at least three proline-directed serines (sp), S795, S807 and S811, which have been reported to be phosphorylated in vivo and which could be targeted by the cdk9 complex. These data suggest that, in logarithmically growing cells, cdk9/cyclin T2 and pRb are located in a nuclear multiprotein complex probably involved in transduction of cellular signals to the basal transcription machinery and that one of these signals could be the cdk9 phosphorylation of pRb.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • 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

Abbreviations

cdk:

cyclin-dependent kinase

GST:

glutathione S-transferase

pRb:

retinoblastoma protein

References

  • Adams PD, Li X, Sellers WR, Baker KB, Leng X, Harper JW, Taya Y, Kaelin WG . 1999 Mol. Cell. Biol. 19: 1068–1080

  • Bagella L, MacLachlan TK, Buono RJ, Pisano MM, Giordano A, De Luca A . 1998 J. Cell. Physiol. 177: 206–213

  • Bagella L, Stiegler P, De Luca A, Siracusa LD, Giordano A . 2000 J. Cell. Biochem. 78: 170–178

  • Corbeil H, Whyte P, Branton P . 1995 Oncogene 11: 909–920

  • Dahmus ME . 1996 J. Biol. Chem. 271: 19009–19012

  • DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huand CM, Lee WH, Marsilio E, Paucha E, Livingston DM . 1998 Cell 54: 257–283

  • De Falco G, Giordano A . 1998 J. Cell. Physiol. 177: 501–506

  • De Falco G, Giordano A . 2002 Cancer Biology and Therapy in press

  • De Falco G, Bagella L, Claudio PP, De Luca A., Fu Y, Calabretta B, Sala A, Giordano A . 2000 Oncogene 19: 373–379

  • De Luca A, Esposito V, Baldi A, Claudio PP, Fu Y, Caputi M, Pisano M, Baldi F, Giordano A . 1997 J. Cell. Physiol. 172: 265–273

  • De Luca P, Majello B, Lania L . 1998 J. Cell Biochem. 70: 281–287

  • Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg R . 1993 Cell 73: 499–511

  • Edwards MC, Wong C, Elledge SJ . 1998 Mol. Cell. Biol. 18: 4291–4300

  • Ezhevsky S, Naggahara H, Vocero-Akbani A, Gius D, Wei M, Dowdy S . 1997 Proc. Natl. Acad. Sci. USA 94: 10699–10704

  • Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J-Y, Livingston . 1993 Cell 73: 487–497

  • Fanciulli M, Bruno T, Di Padova M, De Angelis R, Iezzi S, Iacobini C, Floridi A, Passananti C . 2000 FASEB J. 14: 904–912

  • Foskett SM, Ghose R, Tang DN, Lewis DE, Rice AP . 2001 J. Virol. 75: 1220–1228

  • Grana X, De Luca A, Sang N, Fu Y, Claudio PP, Rosenblatt J, Morgan DO, Giordano A . 1994 Proc. Natl. Acad. Sci. 91: 3834–3838

  • Gu W, Schneider JW, Condorelli G, Kaushal S, Mahadavi S, Nadal-Ginard B . 1993 Cell 72: 309–324

  • Hatakeyama M, Brill J, Fink G, Weinberg R . 1994 Genes Dev. 8: 1759–1771

  • Hollingsworth RE, Hensey CE, Lee W-H . 1993 Curr. Opin. Cell. Biol. 3: 55–62

  • Kanazawa S, Okamoto T, Peterlin BM . 2000 Immunity 12: 61–70

  • Kwak YT, Ivanov D, Guo J, Nee E, Gaynor RB . 1999 J. Mol. Biol. 288: 57–69

  • Lee O-J, Russo AA, Pavletich NP . 1998 Nature 391: 859–865

  • Lis JT, Mason P, Peng J, Price DH, Werner J . 2000 Genes Dev. 11: 2633–2644

  • Lundberg AS, Weinberg RA . 1998 Mol. Cell. Biol. 18: 753–761

  • MacLachlan TK, Sang N, Giordano A . 1995 Crit. Rew. Eukariot. Gene Expr. 5: 127–156

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

  • Mancebo H, Lee G, Flygare J, Tomassini J, Luu P, Zhu Y, Blau C, Hazuda D, Price D, Flores O . 1997 Genes Dev. 11: 2633–2644

  • Marshall N, Peng J, Xie Z, Price D . 1996 J. Biol. Chem. 271: 27176–27183

  • Mittnacht S . 1998 Curr. Opin. Genet. Dev. 8: 21–27

  • Napolitano G, Majello B, Licciardo P, Giordano A, Lania L . 2000 Gene 254: 139–145

  • Novitch BG, Mulligan GJ, Jacks T, Lassar AB . 1996 J. Cell. Biol. 135: 441–456

  • Novitch BG, Spicer DB, Kim PS, Cheung WL, Lassar AB . 1999 Curr. Biol. 9: 449–459

  • Pan W, Sun T, Hoess RH, Grafstrom RH . 1998 Carcinogenesis 19: 765–769

  • Pan W, Cox S, Hoess RH, Grafstrom RH . 2001 Cancer Res. 61: 2885–2891

  • Peng J, Zhu Y, Milton JT, Price DH . 1998 Genes Dev. 12: 755–762

  • Puri PL, Balsano C, Burgio V, Chirillo P, Natoli G, Ricci L, Mattei E, Graessmann A, Levrero M . 1997 Oncogene 14: 1171–1184

  • Puri PL, Sartorelli V . 2000 J. Cell. Physiol. 185: 155–173

  • Qian Y, Luckey C, Horton L, Esser M, Templeton DJ . 1992 Mol. Cell. Biol. 12: 5363–5372

  • Schneider J, Gu W, Zhu L, Mahdavi V, Nadal-Ginard B . 1994 Science 264: 1467–1471

  • Shin E, Shin A, Paulding C, Schaffhausen B, Yee A . 1995 Mol. Cell. Biol. 15: 2252–2262

  • Simone C, Giordano A . 2001 Frontiers in Bioscience 6: 1073–1082

  • Simone C, Stiegler P, Bagella L, Pucci B, Bellan C, De Falco G, De Luca A, Guanti G, Puri PL, Giordano A . 2002 Oncogene 21: 4137–4148

  • Stiegler P, Giordano A . 2001 Crit. Rev. Eukariot. Gene Expr. 11: 59–76

  • Wei P, Gender ME, Fang SM, Fisher WH, Jones KA . 1998 Cell 92: 451–462

  • Welch PJ, Wang JYJ . 1993 Cell 75: 779–790

  • Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E . 1988 Nature 334: 124–129

  • Wimmer J, Fujinaga K, Taube R, Cujec TP, Zhu Y, Peng J, Price DH, Peterlin BM . 1999 Virology 255: 182–189

  • Xiao ZX, Chen J, Levine AJ, Modjtahedi N, Xing J, Sellers WR, Livingston DM . 1995 Nature 375: 694–698

  • Yang X, Hermann HC, Rice AP . 1996 J. Virol. 70: 4576–4584

  • Zhu Y, Pe'ery T, Peng J, Ramanathan Y, Marshall N, Marshall T, Amendt B, Mathews M, Price D . 1997 Genes Dev. 11: 2622–2632

Download references

Acknowledgements

We thank Marie Basso for her editorial assistance in the preparation of the manuscript and Dr Gaia Gallo for her technical support. We thank Dr David Price for generously providing reagents. This work was supported in part by grants from the Sbarro Institute for Cancer Research and Molecular Medicine (to Dr Giordano). Drs Bellan and Bagella are supported by a ‘Dottorato di Ricerca in Patologia Diagnostica Quantitativa’ from the University of Siena. Finally, we thank Letizia Lavermicocca for her encouragement and support. We dedicate this work to the memory of Professor Angelo Carbonara.

Author information

Author notes

  1. Cristiano Simone and Luigi Bagella: C Simone and L Bagella contributed equally to this study.

Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, PA, USA

    Cristiano Simone, Luigi Bagella & Cristiana Bellan

  2. Department of Internal Medicine and Public Medicine, Division of Medical Genetics, University of Bari, Bari, 70124, Italy

    Cristiano Simone

  3. Institute of Pathologic Anatomy and Histology, University of Siena, Siena, 53100, Italy

    Luigi Bagella & Cristiana Bellan

  4. Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, 19122, Pennsylvania, PA, USA

    Antonio Giordano

Authors
  1. Cristiano Simone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luigi Bagella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristiana Bellan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Giordano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simone, C., Bagella, L., Bellan, C. et al. Physical interaction between pRb and cdk9/cyclinT2 complex. Oncogene 21, 4158–4165 (2002). https://doi.org/10.1038/sj.onc.1205511

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205511

Keywords

This article is cited by

Search

Advanced search

Quick links