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| Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation |
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| Author(s): Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM |
| Source: GENES & DEVELOPMENT Volume: 10 Issue: 16 Pages: 1979-1990 Published: AUG 15 1996 |
| Times Cited: 307 References: 43 |
| Abstract: Cyclin E is a mammalian G(1) cyclin that is both required and rate limiting for entry into S phase. The expression of cyclin E is periodic, peaking at the G(1)-S transition and then decaying as S phase progresses. To understand the mechanisms underlying cyclin E periodicity, we have investigated the regulation of cyclin E degradation. We find that cyclin E is degraded by the ubiquitin-proteasome system, and that this degradation is regulated by both cdk2 binding and cdk2 catalytic activity. Free cyclin E is readily ubiquitinated and degraded by the proteasome. Binding to cdk2 protects cyclin E from ubiquitination, and this protection is reversed by cdk2 activity in a process that involves phosphorylation of cyclin E itself. The data are most consistent with a model in which cdk2 activity initiates cyclin E degradation by promoting the disassembly of cyclin E-cdk2 complexes, followed by the ubiquitination and degradation of free cyclin E. |
| Document Type: Article |
| Language: English |
Addresses:
1. FRED HUTCHINSON CANC RES CTR, DIV BASIC SCI, SEATTLE, WA 98104 USA
2. FRED HUTCHINSON CANC RES CTR, DIV CLIN RES, SEATTLE, WA 98104 USA
3. UNIV WASHINGTON, DEPT MED, SEATTLE, WA 98104 USA
4. UNIV WASHINGTON, DEPT RADIAT ONCOL, SEATTLE, WA 98104 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: VF884 |
| ISSN: 0890-9369 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |