TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization.

Tightly controlled duplication of centrosomes, the primary microtubule-organizing centers of animal cells, ensures bipolarity of the mitotic spindle and accurate chromosome segregation. The RING-B-box-coiled coil ubiquitin ligase tripartite motif-containing protein 37 (TRIM37), whose loss is associated with elevated chromosome missegregation and the tumor-prone human developmental disorder Mulibrey nanism, prevents the formation of ectopic spindle poles assembling around structured condensates that contain the centrosomal protein centrobin. Here, we show that TRIM37's tumor necrosis factor receptor-associated factor (TRAF) domain, which is unique in the extended TRIM family, engages peptide motifs in centrobin to suppress condensate formation. TRIM family proteins form antiparallel coiled-coil dimers with RING-B-box domains at each end. Oligomerization resulting from RING-RING interactions and conformational regulation through B-box 2-B-box 2 interfaces are essential for TRIM37 to suppress centrobin condensate formation. These results indicate that, similar to antiviral TRIM ligases, TRIM37 activation is coupled to detection of oligomerized substrates, facilitated by recognition of specific motifs in the substrate, to enforce ubiquitination-mediated clearance of ectopic centrosomal protein assemblies.