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Multivalent tumor suppressor adenomatous polyposis coli promotes Axin biomolecular condensate formation and efficient ?-catenin degradation.

ABSTRACT: The tumor suppressor adenomatous polyposis coli (APC) is frequently mutated in colorectal cancers. APC and Axin are core components of a destruction complex that scaffolds GSK3? and CK1 to earmark ?-catenin for proteosomal degradation. Disruption of APC results in pathologic stabilization of ?-catenin and oncogenesis. However, the molecular mechanism by which APC promotes ?-catenin degradation is unclear. Here, we find that the intrinsically disordered region (IDR) of APC, which contains multiple ?-catenin and Axin interacting sites, undergoes liquid-liquid phase separation (LLPS) in vitro. Expression of the APC IDR in colorectal cells promotes Axin puncta formation and ?-catenin degradation. Our results support the model that multivalent interactions between APC and Axin drives the ?-catenin destruction complex to form biomolecular condensates in cells, which concentrate key components to achieve high efficient degradation of ?-catenin.

SUBMITTER: Li TM 

PROVIDER: S-EPMC7562749 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Multivalent tumor suppressor adenomatous polyposis coli promotes Axin biomolecular condensate formation and efficient β-catenin degradation.

Li Tie-Mei TM   Ren Jing J   Husmann Dylan D   Coan John P JP   Gozani Or O   Chua Katrin F KF  

Scientific reports 20201015 1

The tumor suppressor adenomatous polyposis coli (APC) is frequently mutated in colorectal cancers. APC and Axin are core components of a destruction complex that scaffolds GSK3β and CK1 to earmark β-catenin for proteosomal degradation. Disruption of APC results in pathologic stabilization of β-catenin and oncogenesis. However, the molecular mechanism by which APC promotes β-catenin degradation is unclear. Here, we find that the intrinsically disordered region (IDR) of APC, which contains multipl  ...[more]

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