Abstract
Human apurinic/apyrimidinic endonuclease (APE), also termed redox factor-1 (Ref-1), is a multifunctional protein. However, the role of APE in regulating cell cycle progression and signal transduction pathway remains unrevealed. The APEas-CL3 cells that express an APE anti-sense gene enter M phase earlier and express more Cdc25C protein as comparison with the control Babe-CL3 cells. Under exposure G2 cells to sodium arsenite, the APEas-CL3 cells are more sensitive in the cytotoxicity and more easily to be recovered from the G2 delay as comparison with the Babe-CL3 cells. Arsenite induced G2 delay is correlated to Cdc25C degradation in both cell lines. However, after arsenite removal for 2 to 3 h, the Cdc25C protein levels in APEas-CL3 cells are higher than those in Babe-CL3 cells. Arsenite increases the phosphor-p53Ser15 and phospho-ERK protein levels in Babe-CL3, but not in APEas-CL3 cells. Furthermore, APE can interact with ERK in vitro and in vivo, and the interaction is enhanced by a reducing environment. Taken together, the present results suggest that APE participates in controlling G2/M transitional checkpoint during normal cell cycle progression and against arsenite-induced cell death by facilitating p53Ser15 and ERK phosphorylation mediated via upstream kinases.