Reduction of oligomer size modulates the competition between cluster formation and phase separation of the tumor suppressor SPOP.

ABSTRACT: Phase separation is a ubiquitous process that compartmentalizes many cellular pathways. Given that the same interactions that drive phase separation mediate the formation of complexes below the saturation concentration, the contribution of condensates vs complexes to function is not always clear. Here, we characterized several new cancer-associated mutations of the tumor suppressor Speckle-type POZ protein (SPOP), a substrate recognition subunit of the Cullin3-RING ubiquitin ligase (CRL3), which pointed to a strategy for generating separation-of-function mutations. SPOP self-associates into linear oligomers and interacts with multivalent substrates, and this mediates the formation of condensates. These condensates bear the hallmarks of enzymatic ubiquitination activity. We characterized th

SUBMITTER: Sabri N 

PROVIDER: S-EPMC10054981 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature