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| A NEW REGULATORY MOTIF IN CELL-CYCLE CONTROL CAUSING SPECIFIC-INHIBITION OF CYCLIN-D/CDK4 |
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| Author(s): SERRANO M, HANNON GJ, BEACH D |
| Source: NATURE Volume: 366 Issue: 6456 Pages: 704-707 Published: DEC 16 1993 |
| Times Cited: 2,639 References: 23 |
| 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 retino-blastoma protein. |
| Document Type: Article |
| Language: English |
Addresses:
1. COLD SPRING HARBOR LAB, HOWARD HUGHES MED INST, POB 100, COLD SPRING HARBOR, NY 11724 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: MM265 |
| ISSN: 0028-0836 |
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