The Slingshot Phosphatase SSH3 Is A Novel Anti-apoptotic Factor

The Slingshot phosphatases(SSH1,SSH2,and SSH3) regulate microfilament dynamic assambly though regulation of the phosphorylation status of cofilin. Different with the other two members,SSH3 has little phosphatase activity upon phosphorylated cofilin and does not colocalize with microfilaments.Our data showed that knockdown of SSH3 by small interfering RNA in Hela cells induced apoptosis,as determined by an increase of cleavage of poly(ADP-ribose) polymerase andγ-H2AX. When treated with the apoptosis inducer staurosporine,SSH3-depleted cells had a decrease in proliferation;SSH3 protein was cleaved into small fragments,and this cleavage was blocked by the caspase inhibibter Z-VAD.The cleaved form of SSH3 translocated from cytosol to nuclear and bound to chromatin.In vitro caspase cleavage assays revealed that SSH3 was cleaved by caspase-3 at D80 and D153.We also found that SSH3 co-immunoprecipitated with the apoptosis-inducing factor AIF, and that SSH3 de-phosphorylatedγ-H2AX in vitro.Collectively,these fndings indicate that SSH3 is a novel substrate of caspase 3 and is involved in anti-apoptosis.