M. Fiscella et al., WIP1, A NOVEL HUMAN PROTEIN PHOSPHATASE THAT IS INDUCED IN RESPONSE TO IONIZING-RADIATION IN A P53-DEPENDENT MANNER, Proceedings of the National Academy of Sciences of the United Statesof America, 94(12), 1997, pp. 6048-6053
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.