NDLI: Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription

Content Provider	PubMed Central
Author	Takai, Hiroyuki Naka, Kazuhito Okada, Yuki Watanabe, Miho Harada, Naoki Saito, Shin’ichi Anderson, Carl W. Ettore, Appella Nakanishi, Makoto Suzuki, Hiroshi Nagashima, Kazuo Sawa, Hirofumi Ikeda, Kyoji Motoyama, Noboru
Copyright Year	2002
Abstract	The mammalian Chk2 kinase is thought to mediate ATM-dependent signaling in response to DNA damage. The physiological role of mammalian Chk2 has now been investigated by the generation of Chk2-deficient mice. Although Chk2 –/– mice appeared normal, they were resistant to ionizing radiation (IR) as a result of the preservation of splenic lymphocytes. Thymocytes and neurons of the developing brain were also resistant to IR-induced apoptosis. The IR-induced G1/S cell cycle checkpoint, but not the G2/M or S phase checkpoints, was impaired in embryonic fibroblasts derived from Chk2 –/– mice. IR-induced stabilization of p53 in Chk2 –/– cells was 50–70% of that in wild-type cells. Caffeine further reduced p53 accumulation, suggesting the existence of an ATM/ATR-dependent but Chk2-independent pathway for p53 stabilization. In spite of p53 protein stabilization and phosphorylation of Ser23, p53-dependent transcriptional induction of target genes, such as p21 and Noxa, was not observed in Chk2 –/– cells. Our results show that Chk2 plays a critical role in p53 function in response to IR by regulating its transcriptional activity as well as its stability.
Related Links	http://dx.doi.org/10.1093/emboj/cdf506
Ending Page	5205
Page Count	11
Starting Page	5195
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	19
Volume Number	21
Language	English
Publisher	Oxford University Press
Publisher Date	2002-10-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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