SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression
| Autor: | LeAnn C. Rogers, Stephanie Batalis, Christopher H. Mauney, David A. Ornelles, Wayne O. Hemphill, Thomas Hollis |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chemistry
phosphorylation QH301-705.5 DNA replication protein localization Cell cycle Protein oxidation Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Protein subcellular localization prediction SAMHD1 Cell biology dNTP Phosphorylation Molecular Biosciences protein oxidation cell cycle Biology (General) Molecular Biology Nuclear localization sequence Cellular localization Original Research |
| Zdroj: | Frontiers in Molecular Biosciences, Vol 8 (2021) Frontiers in Molecular Biosciences |
| DOI: | 10.3389/fmolb.2021.724870/full |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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