IMiDs induce FAM83F degradation via an interaction with CK1α to attenuate Wnt signalling.

ABSTRACT: Immunomodulatory imide drugs (IMiDs) bind CRBN, a substrate receptor of the Cul4A E3 ligase complex, enabling the recruitment of neo-substrates, such as CK1α, and their degradation via the ubiquitinproteasome system. Here, we report FAM83F as such a neo-substrate. The eight FAM83 proteins (A-H) interact with and regulate the subcellular distribution of CK1α. We demonstrate that IMiD-induced FAM83F degradation requires its association with CK1α. However, no other FAM83 protein is degraded by IMiDs. We have recently identified FAM83F as a mediator of the canonical Wnt signalling pathway. The IMiD-induced degradation of FAM83F attenuated Wnt signalling in colorectal cancer cells and removed CK1α from the plasma membrane, mirroring the phenotypes observed with genetic ablation of FAM83F. Intri

SUBMITTER: Dunbar K 

PROVIDER: S-EPMC7768194 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature