Methionine Sulfoxide Reductase A Regulates Cell Growth through the p53‐p21 Pathway

Abstract

MsrA is an oxidoreductase that catalyzes the stereospecific reduction of methionine‐S‐sulfoxide to methionine. Although MsrA is well‐characterized as an antioxidant and has been implicated in the aging process and cellular senescence, its roles in cell proliferation are poorly understood. Here, we report a critical role of MsrA in normal cell proliferation and describe the regulation mechanism of cell growth by this protein. Down‐regulation of MsrA inhibited cell proliferation, but MsrA overexpression did not promote it. MsrA deficiency led to an increase in p21, a major cyclin‐dependent kinase inhibitor, thereby causing cell cycle arrest at the G2/M stage. While protein levels of p53 were not altered upon MsrA deficiency, its acetylation level was significantly elevated, which subsequently activated p21 transcription. The data suggest that MsrA is a regulator of cell growth that mediates the p53‐p21 pathway.