Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO J. 2000 Dec 1;19(23):6517-26.

p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation.

Author information

  • 1First Department of Internal Medicine, Sapporo Medical University, School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. takekawa@ims.u-tokyo.ac.jp

Abstract

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 we 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, H(2)O(2) 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.

PMID:
11101524
[PubMed - indexed for MEDLINE]
PMCID:
PMC305857
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk