Cited by 19

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ATP-dependent activation of p21 WAF1/CIP1 -associated Cdk2 by Cdc6

Kan, Qiuming, Jinno, Shigeki, Yamamoto, Hanako, Kobayashi, Kohei, Okayama, Hiroto·2008·Proceedings of the National Academy of Sciences

Abstract

When cells progressing in mid-S phase are damaged with a base-modifying chemical, they arrest in S phase long after the CHK1 checkpoint signal fades out, partly because of p53-mediated long-lasting induction of the cyclin-dependent kinase inhibitor p21 WAF1/CIP1 . We have recently found that enforced expression of Cdc6, the assembler of prereplicative complexes, markedly advances recovery from the prolonged S-phase arrest and reactivation of Cdk2 despite the presence of a high level of induced p21. Here, we report that Cdc6 protein can activate p21-associated Cdk2 in an ATP-dependent manner in vitro . Consistently, Cdc6 mutated for ATPase or a putative cyclin binding motif is no longer able to activate the Cdk2 in vitro or promote reinitiation of S-phase progression and reactivation of Cdk2 in vivo . These results reveal the never anticipated function of Cdc6 and redefine its role in the control of S-phase progression in mammalian cells.

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Metadata

Authors
Kan, Q., Jinno, S., Yamamoto, H., Kobayashi, K., & Okayama, H.
Affiliations
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Venue
Proceedings of the National Academy of Sciences
Published
2008-03-25
Volume
105
Issue
12
Pages
4757-4762
ISSN
  • 0027-8424
  • 1091-6490
Cited by
19
References
2
Language
en

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