Methionine sulfoxide reductase B3 deficiency inhibits cell growth through the activation of p53–p21 and p27 pathways

•MsrB3 depletion inhibits normal cell proliferation.•MsrB3 deficiency activates the cell cycle inhibitors p21 and p27.•MsrB3 deficiency arrests cell cycle at G1 phase.•MsrB3 is a mediator of cell growth. Methionine sulfoxide reductase B3 (MsrB3) is an oxidoreductase in the endoplasmic reticulum that catalyzes the stereospecific reduction of methionine-R-sulfoxide to methionine. Here, we report the critical role and mechanisms of MsrB3 in cell proliferation. The deletion of MsrB3 led to a significant decrease in cell proliferation in mouse embryonic fibroblast (MEF) cells. MsrB3-knockout MEF cells showed increased p53 protein levels, compared to wild-type MEF cells, which subsequently elevated the protein level of cyclin-dependent kinase inhibitor p21. In addition, MsrB3 deficiency enhanced the protein level of p27, another cell cycle regulator, and caused cell cycle arrest at the G1 stage. The inhibitory effect of MsrB3 deficiency on cell proliferation through the activation of p53–p21 and p27 pathways was also confirmed in primary human dermal fibroblasts. Collectively, the data suggest that MsrB3 is a regulator of cell growth through the p53–p21 and p27 pathways.