The effect of Wip1 over-expression on Chk2-dependent apoptosis has also been examined. Chk1 and Chk2 function in apoptosis-signaling pathways, as both proteins phosphorylate p53 and E2F1 and facilitate both p53-independent and p53-dependent apoptosis (69). Phosphorylation of T68 of Chk2 is important for activation of its kinase activity and induction of apoptosis: phosphorylation of this residue was reduced after IR in Wip1-overexpressing cells compared to control cells (70). As anticipated, overexpression of Wip1 inhibited apoptosis by decreasing phosphorylation of Chk2 on T68 and several other sites of phsophorylation following exposure to IR and, furthermore, that Chk2 and Wip1 interact through the (S/T)Q domain of Chk2 and the N-terminal domain of Wip1 (70, 71).
