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

ABSTRACT: 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.

SUBMITTER: Batalis S

PROVIDER: S-EPMC8426622 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Batalis Stephanie S Rogers LeAnn C LC Hemphill Wayne O WO Mauney Christopher H CH Ornelles David A DA Hollis Thomas T

Frontiers in molecular biosciences 20210826

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 ...[more]

PMID: 34513928

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