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| INHIBITION OF CDK2 ACTIVITY IN-VIVO BY AN ASSOCIATED 20K REGULATORY SUBUNIT |
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| Author(s): GU Y, TURCK CW, MORGAN DO |
| Source: NATURE Volume: 366 Issue: 6456 Pages: 707-710 Published: DEC 16 1993 |
| Times Cited: 682 References: 22 |
| Abstract: THE major events of the cell division cycle are triggered by periodic changes in the activity of cyclin-dependent protein kinases (CDKs). In mammals, the members of the CDK family include CDK2 and CDC2, which are thought to be involved in the control of DNA replication and mitosis, respectively1-3. The protein kinase activity of these enzymes is controlled by a complex array of mechanisms4-6. Activation of the CDK catalytic subunit requires association with a positive regulatory subunit (cyclin) and phosphorylation (at Thr 160 in CDK2). This activated complex can be inhibited by additional phosphorylation at Thr 14 and Tyr 15. Here we report the identification of a new mechanism for the regulation of CDK2 activity. We find that CDK2/cyclin complexes in mouse fibroblasts associate tightly with a 20K protein (CAP20). Complexes containing CAP20 were isolated from cell lysates and found to have negligible kinase activity, indicating that CAP20 association in vivo may inhibit CDK2 activity. We purified CAP20 from 3T3 cells and found that low concentrations of the protein completely inhibit the kinase activity of CDK2 in vitro. Thus CAP20 represents a new negative regulatory subunit that inhibits the activity of CDK2/cyclin complexes in mammalian cells. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF SAN FRANCISCO, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA
2. UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA
3. UNIV CALIF SAN FRANCISCO, HOWARD HUGHES MED INST, SAN FRANCISCO, CA 94143 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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