{"doi":"10.3389/fmolb.2021.724870","title":"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.","journal":"Frontiers in Molecular Biosciences","year":2021,"id":183510,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":737918,"name":"LeAnn C. Rogers","orcid":null,"position":1,"is_corresponding":false},{"id":651190,"name":"Wayne O. Hemphill","orcid":"0000-0002-8136-1574","position":2,"is_corresponding":false},{"id":737919,"name":"Christopher H. Mauney","orcid":null,"position":3,"is_corresponding":false},{"id":382448,"name":"David A. Ornelles","orcid":"0000-0002-5151-8382","position":4,"is_corresponding":false},{"id":604632,"name":"Thomas Hollis","orcid":"0000-0002-4996-6346","position":5,"is_corresponding":false},{"id":737236,"name":"Stephanie Batalis","orcid":"0000-0002-6692-0139","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"34513928","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}