Methionine sulfoxide reductase A regulates cell growth through the p53–p21 pathway

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.

► Down-regulation of MsrA inhibits normal cell proliferation.
► MsrA deficiency leads to an increase in p21 by enhanced p53 acetylation.
► Down-regulation of MsrA causes cell cycle arrest at the G2/M stage.
► MsrA is a regulator of cell growth that mediates the p53–p21 pathway.