Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner
AUTOR(ES)
Fiscella, Michele
FONTE
The National Academy of Sciences of the USA
RESUMO
Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and/or apoptosis. IR-induced G1 arrest has been shown to depend on the presence of the tumor suppressor p53, which acts as a transcriptional activator of several genes. p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by both transcription-dependent and -independent mechanisms. Here we report the identification of a novel transcript whose expression is induced in response to IR in a p53-dependent manner, and that shows homology to the type 2C protein phosphatases. We have named this novel gene, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+ dependence and relative insensitivity to okadaic acid. Studies performed in several cell lines revealed that wip1 accumulation following IR correlates with the presence of wild-type p53. The accumulation of wip1 mRNA following IR was rapid and transient, and the protein was localized to the nucleus. Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation. These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20998Documentos Relacionados
- The mdm-2 gene is induced in response to UV light in a p53-dependent manner.
- p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation
- p53-dependent ceramide response to genotoxic stress.
- Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression
- p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1