作者
Tie-Mei Li, Jing Ren, Dylan Husmann, John P Coan, Or Gozani, Katrin F Chua
发表日期
2020/10/15
期刊
Scientific reports
卷号
10
期号
1
页码范围
17425
出版商
Nature Publishing Group UK
简介
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 multiple β-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 β-catenin degradation. Our results support the model that multivalent interactions between APC and Axin drives the β-catenin destruction complex to form biomolecular condensates in cells, which concentrate key components to …
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TM Li, J Ren, D Husmann, JP Coan, O Gozani… - Scientific reports, 2020