Frontiers in Molecular Biosciences (Aug 2021)

SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression

  • Stephanie Batalis,
  • LeAnn C. Rogers,
  • Wayne O. Hemphill,
  • Christopher H. Mauney,
  • David A. Ornelles,
  • Thomas Hollis

DOI
https://doi.org/10.3389/fmolb.2021.724870
Journal volume & issue
Vol. 8

Abstract

Read online

SAMHD1 activity is regulated by a network of mechanisms including phosphorylation, oxidation, oligomerization, and others. Significant questions remain about the effects of phosphorylation on SAMHD1 function and activity. We investigated the effects of a SAMHD1 T592E phosphorylation mimic on its cellular localization, catalytic activity, and cell cycle progression. We found that the SAMHD1 T592E is a catalytically active enzyme that is inhibited by protein oxidation. SAMHD1 T592E is retained in the nucleus at higher levels than the wild-type protein during growth factor-mediated signaling. This nuclear localization protects SAMHD1 from oxidation by cytoplasmic reactive oxygen species. The SAMHD1 T592E phosphomimetic further inhibits the cell cycle S/G2 transition. This has significant implications for SAMHD1 function in regulating innate immunity, antiviral response and DNA replication.

Keywords