2000年
p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation
EMBO Journal
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- 巻
- 19
- 号
- 23
- 開始ページ
- 6517
- 終了ページ
- 6526
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/emboj/19.23.6517
- 出版者・発行元
- OXFORD UNIV PRESS
The stress-responsive p38 MAPK, when activated by genotoxic stresses such as UV radiation, enhances p53 activity by phosphorylation and leads to cell cycle arrest or apoptosis. Here me report that a member of the protein phosphatase type 2C family, Wip1, has a role in down-regulating p38-p53 signaling during the recovery phase of the damaged cells. Wip1 was originally identified as a gene whose expression is induced following gamma or UV radiation in a p53-dependent manner. We found that Wip1 is also inducible by other environmental stresses, such as anisomycin, H2O2 and methyl methane sulfonate. UV-induction of Wip1 requires p38 activity in addition to the wild-type p53. Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue. Furthermore, Wip1 expression attenuates UV-induced p53 phosphorylation at Ser33 and Ser46, residues previously reported to be phosphorylated by p38. Wip1 expression also suppresses both p53-mediated transcription and apoptosis in response to UV radiation. These results suggest that p53-dependent expression of Wip1 mediates a negative feedback regulation of p38-p53 signaling and contributes to suppression of the UV-induced apoptosis.
- リンク情報
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- DOI
- https://doi.org/10.1093/emboj/19.23.6517
- CiNii Articles
- http://ci.nii.ac.jp/naid/80012234924
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/11101524
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000165763800024&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1093/emboj/19.23.6517
- ISSN : 0261-4189
- CiNii Articles ID : 80012234924
- PubMed ID : 11101524
- Web of Science ID : WOS:000165763800024