p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.

Abstract:

:gamma-Irradiation of human diploid fibroblasts in the G1 interval caused arrest of the cell cycle prior to S phase. This cell cycle block was correlated with a lack of activation of both cyclin E-Cyclin-dependent kinase 2 (Cdk2) and cyclin A-Cdk2 kinases and depended on wild-type p53. Although the accumulation of cyclin A was strongly inhibited in gamma-irradiated cells, cyclin E accumulated and bound Cdk2 at normal levels but remained in an inactive state. We found that both whole-cell lysates and inactive cyclin E-Cdk2 complexes prepared from irradiated cells contained an activity capable of inactivating cyclin E-Cdk2 complexes. The protein responsible for this activity was shown to be p21CIP1/WAF1, recently described as a p53-inducible Cdk inhibitor. Our data suggest a model in which ionizing radiation confers G1 arrest via the p53-mediated induction of a Cdk inhibitor protein.

journal_name

Cell

journal_title

Cell

authors

Dulić V,Kaufmann WK,Wilson SJ,Tlsty TD,Lees E,Harper JW,Elledge SJ,Reed SI

doi

10.1016/0092-8674(94)90379-4

subject

Has Abstract

pub_date

1994-03-25 00:00:00

pages

1013-23

issue

6

eissn

0092-8674

issn

1097-4172

pii

0092-8674(94)90379-4

journal_volume

76

pub_type

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