In:
Science, American Association for the Advancement of Science (AAAS), Vol. 287, No. 5459 ( 2000-03-10), p. 1824-1827
Abstract:
Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2 −/− embryonic stem cells failed to maintain γ-irradiation–induced arrest in the G 2 phase of the cell cycle. Chk2 −/− thymocytes were resistant to DNA damage–induced apoptosis. Chk2 −/− cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to γ irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to γ irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.287.5459.1824
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2000
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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