A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

Serrano, M., Hannon, G. J., Beach, D. (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature, 366 (6456). pp. 704-707. ISSN 00280836 (ISSN)

Abstract

THE division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase. 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 protein. 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.

Item Type: Paper
Uncontrolled Keywords: cyclin dependent kinase protein kinase retinoblastoma protein article cell cycle enzyme inhibition gene fusion growth regulation nonhuman priority journal yeast Amino Acid Sequence Base Sequence Carrier Proteins Cloning, Molecular Cyclin D1 Cyclins DNA Glutathione Transferase Hela Cells Human Molecular Sequence Data Oncogene Proteins Phosphorylation Protein Kinases Protein p16 Recombinant Fusion Proteins Saccharomyces cerevisiae Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Eukaryota
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation
organs, tissues, organelles, cell types and functions > cell types and functions
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 1993
Date Deposited: 09 Jan 2013 17:36
Last Modified: 09 Jan 2013 17:36
Related URLs:
URI: https://repository.cshl.edu/id/eprint/26495

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