Unknown

Dataset Information

0

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

Json Xml
altmetric image

Publications

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]

Similar Datasets

Unknown Structural basis of the Axin-adenomatous polyposis coli interaction.
| S-EPMC384355 | biostudies-literature
Unknown Multivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.
| S-EPMC9214244 | biostudies-literature
Unknown Functional comparison of human adenomatous polyposis coli (APC) and APC-like in targeting beta-catenin for degradation.
| S-EPMC3698177 | biostudies-literature
Unknown Neurite outgrowth involves adenomatous polyposis coli protein and beta-catenin.
| S-EPMC3373789 | biostudies-literature
Unknown Characterization of a 60S complex of the adenomatous polyposis coli tumor suppressor protein.
| S-EPMC1808328 | biostudies-literature
Unknown Adenomatous Polyposis Coli Gene Mutations in 22 Chinese Pedigrees with Familial Adenomatous Polyposis.
| S-EPMC6542301 | biostudies-literature
Unknown Adenomatous polyposis coli (APC) regulates miR17-92 cluster through ?-catenin pathway in colorectal cancer.
| S-EPMC4960006 | biostudies-literature
Unknown Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis.
| S-EPMC6236305 | biostudies-literature
Unknown Identification of Endogenous Adenomatous Polyposis Coli Interaction Partners and β-Catenin-Independent Targets by Proteomics.
| S-EPMC7302431 | biostudies-literature
Unknown Tankyrase Inhibitors Stimulate the Ability of Tankyrases to Bind Axin and Drive Assembly of ?-Catenin Degradation-Competent Axin Puncta.
| S-EPMC4773256 | biostudies-literature