The Mechanism of Histone Ubiquitylation by the ASB9-CUL5 Ubiquitin Ligase.

ABSTRACT: The E3 ligase substrate receptor ankyrin and SOCS box protein 9 (ASB9) was shown to bind over 10 different proteins including metabolic enzymes such as creatine kinase, filament proteins such as vimentin, and histones. In previous work, we characterized the ASB9-Cullin 5 E3 ligase (ASB9-CRL) ubiquitylation of creatine kinase and showed that ubiquitylation required the ring-between-ring ligase, ARIH2. Here we characterize the ASB9-CRL ubiquitylation of histones and show that histones H3 and H4 are polyubiquitylated by the ASB9-CRL whereas histones H2A and H2B are not. Many, but not all lysines in the histones are ubiquitylated suggesting some substrate specificity. Binding experiments show that the ligase-histone interaction is highly electrostatic and the neddylated ASB9-CRL binds with hig

SUBMITTER: Lin CP 

PROVIDER: S-EPMC12154916 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature