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

Arch Biochem Biophys

Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu, Republic of Korea. Electronic address:

Published: April 2014

AI Article Synopsis

  • Methionine sulfoxide reductase B3 (MsrB3) is an enzyme in the endoplasmic reticulum that reduces methionine-R-sulfoxide back to methionine and plays a significant role in cell proliferation.
  • Deleting MsrB3 in mouse embryonic fibroblast (MEF) cells resulted in decreased cell growth and increased levels of the tumor suppressor protein p53, which then raised levels of cell cycle inhibitors p21 and p27, leading to cell cycle arrest in the G1 phase.
  • The study shows that MsrB3 is crucial for regulating cell growth by interacting with the p53-p21 and p27 pathways, a finding that was also

Article Abstract

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.

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http://dx.doi.org/10.1016/j.abb.2014.02.008DOI Listing

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