{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Park JE"],"funding":["U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute","NCI NIH HHS"],"pagination":["2017"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10914751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1-5% of CD4<sup>+</sup> T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4's functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr's capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4<sup>+</sup> T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers."],"journal":["Nature communications"],"pubmed_title":["Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4<sup>+</sup> T cells."],"pmcid":["PMC10914751"],"funding_grant_id":["75N91019D00024"],"pubmed_authors":["Zhou M","Narayan K","Park JE","Il Ahn J","Maldarelli F","Kim TS","Alam MS","Shi V","Zeng Y","Strebel K","Lee KS","Ahn J","Ashwell JD","Mikolaj M","Chun TW","Monnie CM"],"additional_accession":[]},"is_claimable":false,"name":"Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4<sup>+</sup> T cells.","description":"HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1-5% of CD4<sup>+</sup> T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4's functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr's capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4<sup>+</sup> T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2024-11-14T16:59:41.914Z","creation":"2024-11-14T16:59:41.914Z"},"accession":"S-EPMC10914751","cross_references":{"pubmed":["38443376"],"doi":["10.1038/s41467-024-46306-8"]}}