WIP1, A NOVEL HUMAN PROTEIN PHOSPHATASE THAT IS INDUCED IN RESPONSE TO IONIZING-RADIATION IN A P53-DEPENDENT MANNER

Exposure of mammalian cells to ionizing radiation (IR) induces a compl ex array of cellular responses including cell cycle arrest and/or apop tosis. IR-induced GI arrest has been shown to depend on the presence o f 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 bath t ranscription-dependent and -independent mechanisms, Here we report the identification of a novel transcript whose expression is induced in r esponse to IR in a p53-dependent manner, and that shows homology to th e type 2C protein phosphatases. We have named this novel gent, wip1. I n vitro, recombinant Wip1 displayed characteristics of a type 2C phosp hatase, including Mg2+ dependence and relative insensitivity to okadai c acid. Studies performed in several cell lines revealed that wip1 acc umulation following IR correlates with the presence of wild-type p53, The accumulation of wip1 mRNA following IR was rapid and transient, an d the protein was localized to the nucleus, Similar to waf1, ectopic e xpression of wip1 in human cells suppressed colony formation, These re sults suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner.