biostudies-literatureKassmeier MDNCRR NIH HHSNIAID NIH HHSNIMH NIH HHSNIGMS NIH HHS945-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC3280554biostudies-literatureUnknown31(4)The N-terminus of full-length RAG1, though dispensable for RAG1/2 cleavage activity, is required for efficient V(D)J recombination. This region supports RING E3 ubiquitin ligase activity in vitro, but whether full-length RAG1 functions as a single subunit or a multi-subunit E3 ligase in vivo is unclear. We show the multi-subunit cullin RING E3 ligase complex VprBP/DDB1/Cul4A/Roc1 associates with full-length RAG1 through VprBP. This complex is assembled into RAG protein-DNA complexes, and supports in-vitro ubiquitylation activity that is insensitive to RAG1 RING domain mutations. Conditional B lineage-specific VprBP disruption arrests B-cell development at the pro-B-to-pre-B cell transition, but this block is bypassed by expressing rearranged immunoglobulin transgenes. Mice with a conditionThe EMBO journalVprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity.PMC32805541S10RR027352R56 AI055599AI055599P30 MH062261R56AI091748-01A1R01 GM067113G20 RR024001R56 AI091748S10 RR027352R01 AI055599G20RR024001Xiong YRaval PJackson SSwanson PCKassmeier MDMondal KCiborowski PAnderson DKPalmer VLKumar SPerry GAfalseVprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity.The N-terminus of full-length RAG1, though dispensable for RAG1/2 cleavage activity, is required for efficient V(D)J recombination. This region supports RING E3 ubiquitin ligase activity in vitro, but whether full-length RAG1 functions as a single subunit or a multi-subunit E3 ligase in vivo is unclear. We show the multi-subunit cullin RING E3 ligase complex VprBP/DDB1/Cul4A/Roc1 associates with full-length RAG1 through VprBP. This complex is assembled into RAG protein-DNA complexes, and supports in-vitro ubiquitylation activity that is insensitive to RAG1 RING domain mutations. Conditional B lineage-specific VprBP disruption arrests B-cell development at the pro-B-to-pre-B cell transition, but this block is bypassed by expressing rearranged immunoglobulin transgenes. Mice with a condition2012-01-01T00:00:00Z2012 Feb2025-04-26T21:01:15.903Z2019-03-27T00:49:13ZS-EPMC32805542215782110.1038/emboj.2011.455