Mesoscale regulation of MTOCs by the E3 ligase TRIM37.

ABSTRACT: Centrosomes ensure accurate chromosome segregation during cell division. Although the regulation of centrosome number is well-established, less is known about the suppression of non-centrosomal MTOCs (ncMTOCs). The E3 ligase TRIM37, implicated in Mulibrey nanism and 17q23-amplified cancers, has emerged as a key regulator of both centrosomes and ncMTOCs. Yet, the mechanism by which TRIM37 achieves enzymatic activation to target these mesoscale structures had remained unknown. Here, we elucidate TRIM37's activation process, beginning with TRAF domain-directed substrate recognition, progressing through B-box domain-mediated oligomerization, and culminating in RING domain dimerization. Using optogenetics, we demonstrate that TRIM37's E3 activity is directly coupled to the assembly state of its

SUBMITTER: Yeow ZY 

PROVIDER: S-EPMC11482927 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature