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
Celljournal_title
Cellauthors
Dulić V,Kaufmann WK,Wilson SJ,Tlsty TD,Lees E,Harper JW,Elledge SJ,Reed SIdoi
10.1016/0092-8674(94)90379-4subject
Has Abstractpub_date
1994-03-25 00:00:00pages
1013-23issue
6eissn
0092-8674issn
1097-4172pii
0092-8674(94)90379-4journal_volume
76pub_type
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