A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 (original) (raw)
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- Published: 16 December 1993
Nature volume 366, pages 704–707 (1993)Cite this article
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Abstract
THE division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs)1,2. The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle3,4. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase3–6. CDK4 exists, in part, as a multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen and a protein, p21 (refs 7–9). CDK4 associates separately with a protein of _M_r 16K, particularly in cells lacking a functional retinoblastoma protein9. Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes. p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein.
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References
- Solomon, M., J. Curr. Opin. Cell Biol. 5, 180–186 (1993).
Article CAS Google Scholar - Nigg, E. A. Curr. Opin. Cell Biol. 5, 187–193 (1993).
Article CAS Google Scholar - Motokura, T. & Arnold, A. Biochim. biophys. Acta 1155, 63–78 (1993).
CAS PubMed Google Scholar - Sherr, C. J. Cell 73, 1059–1065 (1993).
Article CAS Google Scholar - Matsushime, H., Roussel, M. F., Ashmun, R. A. & Sherr, C. J. Cell 65, 701–713 (1991).
Article CAS Google Scholar - Matsushime, H. et al. Cell 71, 323–334 (1992).
Article CAS Google Scholar - Xiong, Y., Shang, H. & Beach, D. Cell 71, 505–514 (1992).
Article CAS Google Scholar - Zhang, H., Xiong, Y. & Beach, D. Molec. biol. Cell 4, 897–906 (1993).
Article CAS Google Scholar - Xiong, Y., Zhang, H. & Beach, D. Genes Dev. 7, 1572–1583 (1993).
Article CAS Google Scholar - Fields, S. & Song, O. Nature 340, 245–246 (1989).
Article ADS CAS Google Scholar - Meyerson, M. et al. EMBO J. 11, 2909–2917 (1992).
Article CAS Google Scholar - Kato, J.-Y., Matsushime, H., Hiebert, S. W., Ewen, M. E. & Sherr, C. J. Genes Dev. 7, 331–342 (1993).
Article CAS Google Scholar - Ewen, M. E. et al. Cell 73, 487–497 (1993).
Article CAS Google Scholar - Zhu, L. et al. Genes Dev. 7, 1111–1125 (1993).
Article CAS Google Scholar - Hannon, G. J., Demetrick, D. & Beach, D. Genes Dev. 7, 2378–2391 (1993).
Article CAS Google Scholar - Li, Y., Graham, C., Lacy, S., Duncan, A. M. V. & Whyte, P. Genes Dev. 7, 2366–2377 (1993).
Article CAS Google Scholar - Lukas, J., Pagano, M., Staskova, Z., Draetta, G. & Bartek, J. Oncogene (in the press).
- Xiong, Y. et al. Nature 366, 701–704 (1993).
Article ADS CAS Google Scholar - Lees, E. M. & Harlow, E. Molec. cell. Biol. 13, 1194–1201 (1993).
Article CAS Google Scholar - Zheng, X.-F. & Ruderman, J. V. Cell 75, 155–164 (1993).
Article CAS Google Scholar - Michaely, P. & Bennet, V. Trends Cell Biol. 2, 127–129 (1992).
Article CAS Google Scholar - Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Habor Laboratory Press, New York, 1988).
Google Scholar - Chen, X.-S., Brash, A. R. & Funk, C. D. Eur. J. Biochem. 214, 845–852 (1993).
Article CAS Google Scholar
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Author notes
- David Beach: To whom correspondence should be addressed.
Authors and Affiliations
- Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, 11724, USA
Manual Serrano, Gregory J. Hannon & David Beach
Authors
- Manual Serrano
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Serrano, M., Hannon, G. & Beach, D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.Nature 366, 704–707 (1993). https://doi.org/10.1038/366704a0
- Received: 12 November 1993
- Accepted: 01 December 1993
- Issue Date: 16 December 1993
- DOI: https://doi.org/10.1038/366704a0
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