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

被引：17

作者：

Li, Tie-Mei ^{[1
,2
,3
]}

Ren, Jing ^{[3
]}

Husmann, Dylan ^{[2
]}

Coan, John P. ^{[2
]}

Gozani, Or ^{[2
]}

Chua, Katrin F. ^{[1
,4
,5
]}

机构：

[1] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[3] MRC, Lab Mol Biol, Cambridge CB2 0QH, England

[4] Vet Affairs Palo Alto Hlth Care Syst, Educ, Palo Alto, CA 94304 USA

[5] Vet Affairs Palo Alto Hlth Care Syst, Clin Ctr, Geriatr Res, Palo Alto, CA 94304 USA

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

关键词：

PHASE-SEPARATION; APC; PROTEIN; MUTATIONS; COMPLEX; BINDING; PHOSPHORYLATION; DOMAIN; ROLES; IMAGE;

D O I：

10.1038/s41598-020-74080-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta and CK1 to earmark beta -catenin for proteosomal degradation. Disruption of APC results in pathologic stabilization of beta -catenin and oncogenesis. However, the molecular mechanism by which APC promotes beta -catenin degradation is unclear. Here, we find that the intrinsically disordered region (IDR) of APC, which contains multiple beta -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 beta -catenin degradation. Our results support the model that multivalent interactions between APC and Axin drives the beta -catenin destruction complex to form biomolecular condensates in cells, which concentrate key components to achieve high efficient degradation of beta -catenin.

引用

页数：9

共 46 条

[1] Axin-mediated CKI phosphorylation of β-catenin at Ser 45:: a molecular switch for the Wnt pathway [J].