SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression
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 cel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.724870/full |
| _version_ | 1829137058664284160 |
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| author | Stephanie Batalis LeAnn C. Rogers Wayne O. Hemphill Christopher H. Mauney David A. Ornelles Thomas Hollis |
| author_facet | Stephanie Batalis LeAnn C. Rogers Wayne O. Hemphill Christopher H. Mauney David A. Ornelles Thomas Hollis |
| author_sort | Stephanie Batalis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T18:52:19Z |
| format | Article |
| id | doaj.art-fd22dab9fa0f4b24a6f31374dd0f7ad9 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-14T18:52:19Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-fd22dab9fa0f4b24a6f31374dd0f7ad92022-12-21T22:51:13ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.724870724870SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase ProgressionStephanie Batalis0LeAnn C. Rogers1Wayne O. Hemphill2Christopher H. Mauney3David A. Ornelles4Thomas Hollis5Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United StatesSAMHD1 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.724870/fullSAMHD1phosphorylationprotein localizationprotein oxidationcell cycledNTP |
| spellingShingle | Stephanie Batalis LeAnn C. Rogers Wayne O. Hemphill Christopher H. Mauney David A. Ornelles Thomas Hollis SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression Frontiers in Molecular Biosciences SAMHD1 phosphorylation protein localization protein oxidation cell cycle dNTP |
| title | SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression |
| title_full | SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression |
| title_fullStr | SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression |
| title_full_unstemmed | SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression |
| title_short | SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression |
| title_sort | samhd1 phosphorylation at t592 regulates cellular localization and s phase progression |
| topic | SAMHD1 phosphorylation protein localization protein oxidation cell cycle dNTP |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.724870/full |
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