| | |  | | | | Record from Web of Science® | | | | | | |
| Cooperating oncogenes converge to regulate cyclin/cdk complexes |
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| Author(s): Lloyd AC, Obermuller F, Staddon S, Barth CF, McMahon M, Land H |
| Source: GENES & DEVELOPMENT Volume: 11 Issue: 5 Pages: 663-677 Published: MAR 1 1997 |
| Times Cited: 170 References: 73 |
| Abstract: The cooperation of oncogenes in the transformation of primary rat Schwann cells is a strikingly synergistic process. We have explored the molecular mechanisms involved. Activation of an inducible Raf kinase results in morphologically transformed cells that are arrested in G(1), via the induction of p21(Cip1) and subsequent inhibition of cyclin/cdk activity. In contrast, coexpression of SV40 large T (LT) or a dominant-negative mutant of p53 abolishes p21(Cip1) induction and alleviates the growth arrest. Moreover in this scenario, Raf activation results in an increase in the specific activity of cyclin/cdk complexes with Raf and LT cooperating to superinduce cyclin A/cdk2 activity and stimulate proliferation in the absence of mitogens. Thus, signaling by Raf and its cooperating partners converges at the regulation of cyclin/cdk complexes, with the cellular responses to Raf modulated by p53. |
| Document Type: Article |
| Language: English |
Addresses:
1. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND
2. DNAX RES INST MOL & CELLULAR BIOL INC, PALO ALTO, CA 94304 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: WP685 |
| ISSN: 0890-9369 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |