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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.

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Abbreviations

cdk:

cyclin-dependent kinase

GST:

glutathione S-transferase

pRb:

retinoblastoma protein

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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.

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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

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  1. Cristiano Simone
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Correspondence to Antonio Giordano.

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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

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