The CUL4B-based E3 ubiquitin ligase regulates mitosis and brain development by recruiting phospho-specific DCAFs

ABSTRACT: The paralogs CUL4A and CUL4B assemble cullin-RING E3 ubiquitin ligase (CRL) complexes regulating multiple chromatin-associated cellular functions. Although they are structurally similar, we found that the unique N-terminal extension of CUL4B is heavily phosphorylated during mitosis, and the phosphorylation pattern is perturbed in the CUL4B-P50L mutation causing X-linked intellectual disability (XLID). Phenotypic characterization and mutational analysis revealed that CUL4B phosphorylation is required for efficient progression through mitosis, controlling spindle positioning and cortical tension. While CUL4B phosphorylation triggers chromatin exclusion, it promotes binding to actin regulators and to two previously unrecognized CUL4B-specific substrate receptors (DCAFs), LIS1 and WDR1. Indee

SUBMITTER: Anna Stier 

PROVIDER: S-SCDT-10_15252-EMBJ_2022112847 | biostudies-other |

REPOSITORIES: biostudies-other