Wip1 was originally identified as a nuclear phosphatase induced in a p53-dependent manner after IR exposure (3). It is a member of the PP2C family of serine/threonine phosphatases, which by definition means it is magnesium-dependent and okadaic acid-insensitive (3). Expression of Wip1 is induced by a variety of stresses, such as exposure to ionizing radiation (IR), ultraviolet (UV) radiation, anisomycin, hydrogen peroxide (H2O2), methyl methane sulfonate, and inflammatory cytokines (3–6). Once induced, Wip1 directly binds to and dephosphorylates several key signaling proteins involved in stress signaling. Some examples of Wip1 targets include p38 MAPK, p53, the phosphorylated form of the histone 2A variant H2AX (gamma-H2AX) and ataxia-telangiectasia mutated (ATM), which play important roles in apoptosis, cell cycle arrest, and DNA repair (4, 7–10).
