{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yi J"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS"],"pagination":["1941"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10079682"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Since Mdm2 (Mouse double minute 2) inhibitors show serious toxicity in clinic studies, different approaches to achieve therapeutic reactivation of p53-mediated tumor suppression in cancers need to be explored. Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as an important pathway for p53 regulation. Like Mdm2, VPRBP is a potent repressor of p53 but VPRBP stability is controlled by USP2. Interestingly, the USP2-VPRBP axis also regulates PD-L1 (programmed death-ligand 1) expression. Strikingly, the combination of a small-molecule USP2 inhibitor and anti-PD1 monoclonal antibody leads to complete regression of the tumors expressing wild-type p53. In contrast to Mdm2, knockout of Usp2 in mice has no obvious effect in normal tissues. More"],"journal":["Nature communications"],"pubmed_title":["Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy."],"pmcid":["PMC10079682"],"funding_grant_id":["R35CA253059","R01 CA258390","R01 CA254970","R01 CA227450","CA227450","RO1CA258390","RO1CA254970","R35 CA253059","P30 CA013696"],"pubmed_authors":["Yi J","Li H","Wang D","Gu W","Baer RJ","Tavana O"],"additional_accession":[]},"is_claimable":false,"name":"Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy.","description":"Since Mdm2 (Mouse double minute 2) inhibitors show serious toxicity in clinic studies, different approaches to achieve therapeutic reactivation of p53-mediated tumor suppression in cancers need to be explored. Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as an important pathway for p53 regulation. Like Mdm2, VPRBP is a potent repressor of p53 but VPRBP stability is controlled by USP2. Interestingly, the USP2-VPRBP axis also regulates PD-L1 (programmed death-ligand 1) expression. Strikingly, the combination of a small-molecule USP2 inhibitor and anti-PD1 monoclonal antibody leads to complete regression of the tumors expressing wild-type p53. In contrast to Mdm2, knockout of Usp2 in mice has no obvious effect in normal tissues. More","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-04-30T13:04:53.291Z","creation":"2024-11-21T02:02:18.611Z"},"accession":"S-EPMC10079682","cross_references":{"pubmed":["37024504"],"doi":["10.1038/s41467-023-37617-3"]}}