Wnt信号通路
葛兰素史克-3
酪蛋白激酶1
生物
大肠腺瘤性息肉病
细胞生物学
连环素
支架蛋白
多蛋白复合物
磷酸化
蛋白激酶A
连环蛋白
信号转导
生物化学
遗传学
癌症
基因
结直肠癌
作者
Junxiu Nong,Kexin Kang,Qiaoni Shi,Xinhui Zhu,Qinghua Tao,Ye-Guang Chen
标识
DOI:10.1083/jcb.202012112
摘要
In Wnt/β-catenin signaling, the β-catenin protein level is deliberately controlled by the assembly of the multiprotein β-catenin destruction complex composed of Axin, adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), and others. Here we provide compelling evidence that formation of the destruction complex is driven by protein liquid–liquid phase separation (LLPS) of Axin. An intrinsically disordered region in Axin plays an important role in driving its LLPS. Phase-separated Axin provides a scaffold for recruiting GSK3β, CK1α, and β-catenin. APC also undergoes LLPS in vitro and enhances the size and dynamics of Axin phase droplets. The LLPS-driven assembly of the destruction complex facilitates β-catenin phosphorylation by GSK3β and is critical for the regulation of β-catenin protein stability and thus Wnt/β-catenin signaling.
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