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PMID: 9418901 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nuclear accumulation of p21Cip1 at the onset of mitosis: a role at the G2/M-phase transition.

Molecular and cellular biology ·Vol. 18 ·No. 1 ·1998-01-00 ·Pages 546-57

Dulić V, Stein GH, Far DF, Reed SI

Abstract

Cell cycle arrest in G1 in response to ionizing radiation or senescence is believed to be provoked by inactivation of G1 cyclin-cyclin-dependent kinases (Cdks) by the Cdk inhibitor p21(Cip1/Waf1/Sdi1). We provide evidence that in addition to exerting negative control of the G1/S phase transition, p21 may play a role at the onset of mitosis. In nontransformed fibroblasts, p21 transiently reaccumulates in the nucleus near the G2/M-phase boundary, concomitant with cyclin B1 nuclear translocation, and associates with a fraction of cyclin A-Cdk and cyclin B1-Cdk complexes. Premitotic nuclear accumulation of cyclin B1 is not detectable in cells with low p21 levels, such as fibroblasts expressing the viral human papillomavirus type 16 E6 oncoprotein, which functionally inactivates p53, or in tumor-derived cells. Moreover, synchronized E6-expressing fibroblasts show accelerated entry into mitosis compared to wild-type cells and exhibit higher cyclin A- and cyclin B1-associated kinase activities. Finally, primary embryonic fibroblasts derived from p21-/- mice have significantly reduced numbers of premitotic cells with nuclear cyclin B1. These data suggest that p21 promotes a transient pause late in G2 that may contribute to the implementation of late cell cycle checkpoint controls.

MeSH Terms
Cell Nucleus/metabolism Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins/metabolism Fibroblasts/cytology,metabolism G2 Phase Humans Mitosis
Chemicals
CDKN1A protein, human Cyclin-Dependent Kinase Inhibitor p21 Cyclins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dulić V
CNRS-UMR 134, Université de Nice-Sophia Antipolis, Nice, France. [email protected]
Stein G H
Far D F
Reed S I
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44 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.1.546
Email
[email protected]
Published
1998-01-00
Pages
546-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121522
Subset
IM
Grants
NIGMS NIH HHS · GM46004 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.1.546 PMC Full Text View journal details
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