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| CELL-CYCLE INHIBITION BY INDEPENDENT CDK AND PCNA BINDING DOMAINS IN P21(CIP1) |
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| Author(s): LUO Y, HURWITZ J, MASSAGUE J |
| Source: NATURE Volume: 375 Issue: 6527 Pages: 159-161 Published: MAY 11 1995 |
| Times Cited: 407 References: 19 |
| Abstract: MAMMALIAN cell-cycle control by antimitogenic signals involves p21(Cip1/WAF1) (refs 1-4), p27(Kip1) (refs 5, 6) and p57(Kip2) (refs 7, 8), a family of proteins that bind to and inhibit cyclin-dependent kinases (CDKs) required for initiation of S phase. The protein p21 also binds to the DNA polymerase 6 processivity factor, proliferating-cell nuclear antigen (PCNA), and inhibits in vitro PCNA-dependent DNA replication(9,10). The CDK and PCNA inhibitory activities of p21 are shown here to be functionally independent and to reside in separate protein domains. The PCNA binding and inhibitory activities, which are not observed with p27 or p57, reside in the C-terminal domain of p21, whereas the CDK inhibitory activity resides in the conserved N-terminal domains of these proteins. When separately overexpressed in mammalian cells, the CDK and PCNA inhibitory domains prevent DNA replication, demonstrating a dual function of p21 as a cell-cycle inhibitor in vivo. |
| Document Type: Article |
| Language: English |
Addresses:
1. MEM SLOAN KETTERING CANC CTR, CELL BIOL & GENET PROGRAM, NEW YORK, NY 10021 USA
2. MEM SLOAN KETTERING CANC CTR, PROGRAM MOLEC BIOL, NEW YORK, NY 10021 USA
3. MEM SLOAN KETTERING CANC CTR, HOWARD HUGHES MED INST, NEW YORK, NY 10021 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QX741 |
| ISSN: 0028-0836 |
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