MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification.

ABSTRACT: C-terminal to LisH (CTLH) E3 ubiquitin ligase complexes regulate a broad range of biological processes and forms separate supramolecular CTLH-MKLN1 and CTLH-WDR26 assemblies possessing distinct substrate specificities. Our previous work revealed that the CTLH complex utilizes the FAM72A substrate adaptor to ubiquitinate and degrade the uracil-DNA glycosylase 2 (UNG2) base excision repair factor. This outcome in B cells permits deoxyuridine mutations catalyzed by activation-induced cytidine deaminase (AID) to persist toward mutational outcomes and drive antibody diversification events. Here, we report that Mkln1-/- mice specifically lacking assembly of CTLH-MKLN1 complexes display reduced somatic hypermutation and class switch recombination frequencies due to increased UNG2, similar to Fam7

SUBMITTER: Barbulescu P 

PROVIDER: S-EPMC12576123 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature