{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:52:24Z","timestamp":1787237544774,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Le Moyne College"},{"id":[{"id":"https:\/\/ror.org\/00q369629","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Le Moyne College Research and Development Committee"},{"id":[{"id":"https:\/\/ror.org\/00q369629","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Le Moyne College Student Research Committee"},{"id":[{"id":"https:\/\/ror.org\/00q369629","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Le Moyne College Ignite Fellowship"},{"id":[{"id":"https:\/\/ror.org\/00q369629","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Walter L. \u201866 and MaryAnne Poland Jesuit Center for Research and Teaching Innovation fund"},{"name":"the Le Moyne College Department of Biological and Environmental Sciences"},{"id":[{"id":"https:\/\/ror.org\/00q369629","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Sulforaphane (SFN), a natural compound found in cruciferous vegetables, mobilizes the transcription factor NRF2 to protect macrophages from HIV-1. SFN\/NRF2 exerts this protective effect by promoting the reduced phosphorylation of the antiviral protein SAMHD1. Phosphorylation at threonine 592 (T592) potently inhibits the capacity of SAMHD1 to restrict HIV-1. How SFN, and other NRF2 mobilizers reduce SAMHD1 T592 phosphorylation is unclear. p21 (CDKN1A) is an NRF2-responsive protein that accumulates in primary macrophages after SFN treatment. p21 blocks SAMHD1 T592 phosphorylation through the inhibition of several cyclin-dependent kinases. We therefore hypothesized that SFN acts through p21 to reduce SAMHD1 T592 phosphorylation in macrophages. Here, we use RNAi, CRISPR-Cas9, and pharmacological inhibition to deplete or delete p21 in macrophages and demonstrate that p21 is necessary for SFN to efficiently reduce SAMHD1 T592 phosphorylation and restrict HIV-1 transduction.<\/jats:p>","DOI":"10.3390\/biom16081213","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:48:31Z","timestamp":1787219311000},"page":"1213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages"],"prefix":"10.3390","volume":"16","author":[{"given":"Bianka Nicolle Pena","family":"Marcelino","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"},{"name":"Department of Psychology, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiersten","family":"Girard","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Letourneau","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Presicci","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Reistrom","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. John","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, Le Moyne College, 1419 Salt Springs Road, Syracuse, NY 13214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0030225","DOI":"10.1128\/jvi.00302-25","article-title":"DNTP Depletion and beyond: The Multifaceted Nature of SAMHD1-Mediated Viral Restriction","volume":"99","author":"Cheung","year":"2025","journal-title":"J. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dobransky, A., Root, M., Hafner, N., Marcum, M., and Sharifi, H.J. (2024). CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X. Viruses, 16.","DOI":"10.3390\/v16081313"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Deutschmann, J., and Gramberg, T. (2021). SAMHD1 \u2026 and Viral Ways around It. Viruses, 13.","DOI":"10.3390\/v13030395"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Coggins, S.A., Mahboubi, B., Schinazi, R.F., and Kim, B. (2020). SAMHD1 Functions and Human Diseases. Viruses, 12.","DOI":"10.3390\/v12040382"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00109-021-02131-w","article-title":"SAMHD1 in Cancer: Curse or Cure?","volume":"100","author":"Schott","year":"2022","journal-title":"J. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3892\/ol.2021.12712","article-title":"Dual Roles of SAMHD1 in Tumor Development and Chemoresistance to Anticancer Drugs","volume":"21","author":"Chen","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tifs.2017.02.002","article-title":"KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane","volume":"69","author":"Fahey","year":"2017","journal-title":"Trends Food Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Furuya, A.K., Sharifi, H.J., Jellinger, R.M., Cristofano, P., Shi, B., and de Noronha, C.M. (2016). Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005581"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.virol.2021.01.008","article-title":"XCT\/SLC7A11 Antiporter Function Inhibits HIV-1 Infection","volume":"556","author":"Rabinowitz","year":"2021","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e0118722","DOI":"10.1128\/jvi.01187-22","article-title":"Sulforaphane Reduces SAMHD1 Phosphorylation To Protect Macrophages from HIV-1 Infection","volume":"96","author":"Sharifi","year":"2022","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kreis, N.-N., Louwen, F., and Yuan, J. (2019). The Multifaceted P21 (Cip1\/Waf1\/CDKN1A) in Cell Differentiation, Migration and Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11091220"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/emboj\/18.5.1223","article-title":"Apoptosis Inhibitory Activity of Cytoplasmic P21(Cip1\/WAF1) in Monocytic Differentiation","volume":"18","author":"Asada","year":"1999","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1172\/JCI83404","article-title":"P21 Mediates Macrophage Reprogramming through Regulation of P50-P50 NF-\u039aB and IFN-\u03b2","volume":"126","author":"Rackov","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 Polarization","volume":"877","author":"Yunna","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, L., and He, C. (2022). Nrf2-Mediated Anti-Inflammatory Polarization of Macrophages as Therapeutic Targets for Osteoarthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.967193"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.4161\/cc.8.20.9565","article-title":"Nrf2 and P21 Regulate the Fine Balance between Life and Death by Controlling ROS Levels","volume":"8","author":"Villeneuve","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11010-020-03901-9","article-title":"Role of Nrf2 in Cell Senescence Regulation","volume":"476","author":"Yuan","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/eji.200838676","article-title":"Regulation of Macrophage Activation and Septic Shock Susceptibility via P21(WAF1\/CIP1)","volume":"39","author":"Trakala","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E1322\u20131324","DOI":"10.1073\/pnas.1322059111","article-title":"P21 Regulates the HIV-1 Restriction Factor SAMHD1","volume":"111","author":"Pauls","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01324-17","DOI":"10.1128\/JVI.01324-17","article-title":"P21 Restricts HIV-1 in Monocyte-Derived Dendritic Cells through the Reduction of Deoxynucleoside Triphosphate Biosynthesis and Regulation of SAMHD1 Antiviral Activity","volume":"91","author":"Allouch","year":"2017","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1089\/107999099312812","article-title":"IFN-Gamma Induction of P21(WAF1) Is Required for Cell Cycle Inhibition and Suppression of Apoptosis","volume":"19","author":"Hobeika","year":"1999","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_23","first-page":"171","article-title":"Interferon-Gamma-Activated Monocytes Impair Infectivity of HIV Particles by an Oxygen Metabolite-Dependent Reaction","volume":"78","author":"Ennen","year":"1993","journal-title":"Immunology"},{"key":"ref_24","first-page":"e66077","article-title":"Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System","volume":"218","author":"Deragon","year":"2025","journal-title":"J. Vis. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"L138","DOI":"10.1152\/ajplung.00075.2017","article-title":"Immunomodulators Targeting MARCO Expression Improve Resistance to Postinfluenza Bacterial Pneumonia","volume":"313","author":"Wu","year":"2017","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jnutbio.2019.01.019","article-title":"Sulforaphane Triggers a Functional Elongation of Microglial Process via the Akt Signal","volume":"67","author":"Wu","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11352","DOI":"10.1074\/jbc.M109062200","article-title":"AKT\/PKB Phosphorylation of P21Cip\/WAF1 Enhances Protein Stability of P21Cip\/WAF1 and Promotes Cell Survival","volume":"277","author":"Li","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/35060032","article-title":"Cytoplasmic Localization of P21Cip1\/WAF1 by Akt-Induced Phosphorylation in HER-2\/Neu-Overexpressing Cells","volume":"3","author":"Zhou","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1038\/nm.2964","article-title":"SAMHD1 Restricts HIV-1 Infection in Resting CD4(+) T Cells","volume":"18","author":"Baldauf","year":"2012","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6944","DOI":"10.1128\/JVI.00241-14","article-title":"Cullin4A and Cullin4B Are Interchangeable for HIV Vpr and Vpx Action through the CRL4 Ubiquitin Ligase Complex","volume":"88","author":"Sharifi","year":"2014","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1161\/01.CIR.0000148681.01282.89","article-title":"Absence of P21Waf1\/Cip1\/Sdi1 Modulates Macrophage Differentiation and Inflammatory Response and Protects against Atherosclerosis","volume":"110","author":"Merched","year":"2004","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrd3010","article-title":"Recognizing and Avoiding SiRNA Off-Target Effects for Target Identification and Therapeutic Application","volume":"9","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2008.09.013","article-title":"Sulforaphane Suppresses TNF-Alpha-Mediated Activation of NF-KappaB and Induces Apoptosis through Activation of Reactive Oxygen Species-Dependent Caspase-3","volume":"274","author":"Moon","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ruhee, R.T., Ma, S., and Suzuki, K. (2019). Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages. Antioxidants, 8.","DOI":"10.3390\/antiox8120577"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fernandez-Prades, L., Brasal-Prieto, M., Alba, G., Martin, V., Montserrat-de la Paz, S., Cejudo-Guillen, M., Santa-Maria, C., Dakhaoui, H., Granados, B., and Sobrino, F. (2023). Sulforaphane Reduces the Chronic Inflammatory Immune Response of Human Dendritic Cells. Nutrients, 15.","DOI":"10.20944\/preprints202306.0318.v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.trsl.2021.01.008","article-title":"Activation of P21 Limits Acute Lung Injury and Induces Early Senescence after Acid Aspiration and Mechanical Ventilation","volume":"233","author":"Huidobro","year":"2021","journal-title":"Transl. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Livingstone, T.L., Saha, S., Bernuzzi, F., Savva, G.M., Troncoso-Rey, P., Traka, M.H., Mills, R.D., Ball, R.Y., and Mithen, R.F. (2022). Accumulation of Sulforaphane and Alliin in Human Prostate Tissue. Nutrients, 14.","DOI":"10.3390\/nu14163263"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.1017\/jns.2025.10033","article-title":"Sulforaphane as a Potential Therapeutic Agent: A Comprehensive Analysis of Clinical Trials and Mechanistic Insights","volume":"14","author":"Saito","year":"2025","journal-title":"J. Nutr. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/carcin\/bgm049","article-title":"Preclinical and Clinical Evaluation of Sulforaphane for Chemoprevention in the Breast","volume":"28","author":"Cornblatt","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4161\/cbt.23374","article-title":"A Novel P21 Attenuator Which Is Structurally Related to Sorafenib","volume":"14","author":"Wettersten","year":"2013","journal-title":"Cancer Biol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E3062","DOI":"10.1073\/pnas.1411370111","article-title":"Synergistic Tumor Suppression by Combined Inhibition of Telomerase and CDKN1A","volume":"111","author":"Gupta","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"988","DOI":"10.7150\/jca.48282","article-title":"UC2288 Induces Cell Apoptosis of Nasopharyngeal Carcinoma Cells via Inhibiting EGFR\/ERK Pathway","volume":"12","author":"Liang","year":"2021","journal-title":"J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1158\/0008-5472.CAN-04-1443","article-title":"BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF\/MEK\/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis","volume":"64","author":"Wilhelm","year":"2004","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.18632\/oncotarget.754","article-title":"NRF2 and P53: Januses in Cancer?","volume":"3","author":"Rotblat","year":"2012","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1089\/ars.2010.3216","article-title":"When NRF2 Talks, Who\u2019s Listening?","volume":"13","author":"Wakabayashi","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1101\/gad.319905","article-title":"A Mechanism of Ubiquitin-Independent Proteasomal Degradation of the Tumor Suppressors P53 and P73","volume":"19","author":"Asher","year":"2005","journal-title":"Genes Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1093\/nar\/30.11.2340","article-title":"Redox State of Tumor Suppressor P53 Regulates Its Sequence-Specific DNA Binding in DNA-Damaged Cells by Cysteine 277","volume":"30","author":"Buzek","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","article-title":"Direct Interaction between Nrf2 and P21(Cip1\/WAF1) Upregulates the Nrf2-Mediated Antioxidant Response","volume":"34","author":"Chen","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4161\/cc.10.6.15012","article-title":"P21(WAF1) Is Component of a Positive Feedback Loop That Maintains the P53 Transcriptional Program","volume":"10","author":"Pang","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1126\/science.272.5262.719","article-title":"Cell Growth Arrest and Induction of Cyclin-Dependent Kinase Inhibitor P21 WAF1\/CIP1 Mediated by STAT1","volume":"272","author":"Chin","year":"1996","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1742-4690-9-49","article-title":"Role of SAMHD1 Nuclear Localization in Restriction of HIV-1 and SIVmac","volume":"9","author":"White","year":"2012","journal-title":"Retrovirology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s12250-021-00351-5","article-title":"Role of Intracellular Distribution of Feline and Bovine SAMHD1 Proteins in Lentiviral Restriction","volume":"36","author":"Wang","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.celrep.2017.08.008","article-title":"SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination","volume":"20","author":"Daddacha","year":"2017","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41586-018-0050-1","article-title":"SAMHD1 Acts at Stalled Replication Forks to Prevent Interferon Induction","volume":"557","author":"Coquel","year":"2018","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1080\/15384101.2017.1314407","article-title":"SAMHD1 Protects Cancer Cells from Various Nucleoside-Based Antimetabolites","volume":"16","author":"Herold","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Arnold, L.H., Groom, H.C.T., Kunzelmann, S., Schwefel, D., Caswell, S.J., Ordonez, P., Mann, M.C., Rueschenbaum, S., Goldstone, D.C., and Pennell, S. (2015). Phospho-Dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005194"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1093\/nar\/gkac573","article-title":"Phosphorylation of SAMHD1 Thr592 Increases C-Terminal Domain Dynamics, Tetramer Dissociation and SsDNA Binding Kinetics","volume":"50","author":"Orris","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1213\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:12:27Z","timestamp":1787220747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":57,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biom16081213"],"URL":"https:\/\/doi.org\/10.3390\/biom16081213","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}