Proteomics

Dataset Information

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The CRL4B E3 ubiquitin ligase complex regulates mitosis by recruiting phospho-specific DCAFs


ABSTRACT: The cullin scaffolds CUL4A and CUL4B assemble E3-ligase complexes regulating multiple mostly 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 this pattern is perturbed in CUL4B-P50L XLID patients. Indeed, phenotypic characterization and mutational analysis revealed that CUL4B phosphorylation is required for efficient progression through mitosis, controlling spindle positioning and cortical tension. Interestingly, while CUL4B phosphorylation triggers chromatin exclusion, it also promotes binding to actin regulators and two unconventional DCAFs, LIS1 and WDR1. Indeed, LIS1 and WDR1 directly bind DDB1, but their binding is enhanced by phosphorylation-dependent interactions with the unique amino terminal domain of CUL4B. Together, our studies uncover specific functions of CRL4B in mitosis, and identify previously unrecognized DCAFs that bind CUL4B by a phosphorylation-dependent mechanism.

INSTRUMENT(S): Q Exactive Plus, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Hela Cell

SUBMITTER: Petra Beli  

LAB HEAD: Petra Beli

PROVIDER: PXD035329 | Pride | 2023-06-15

REPOSITORIES: Pride

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