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APC突变破坏了由Axin相分离组织的β-catenin破坏复杂凝聚物

Dan Zhang^1,2,3, Qi-Qi Ni^1,2,3, Shu-Yang Wang^1,2,3

¹Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Cellular and molecular life sciences : CMLS

|January 26, 2024

概括

由素驱动的相分离形成了β-catenin破坏复合体. 野生型APC稳定了这些凝聚物,而结直肠癌 (CRC) 的突变破坏了这一点,影响了Wnt信号传输.

科学领域:

细胞生物学细胞生物学
分子瘤学分子瘤学
生物化学生物化学

背景情况:

Wnt/β-catenin通路调节细胞命运,在发育过程中至关重要.
异常的Wnt信号传递,特别是由于APC基因突变,驱动着结直肠癌 (CRC) 的发病.
液-液相分离 (LLPS) 越来越被认为是组织细胞过程的机制.

研究的目的:

通过Axin相分离阐明β-catenin破坏复杂凝缩物形成的分子机制.
调查腺多样性肠杆菌 (APC) 基因突变对结直肠癌 (CRC) 中这些凝聚物的影响.
了解Axin驱动的相分离如何影响β-catenin局部化和Wnt通路活性.

主要方法:

细胞成像和生物化学测试,观察凝结物形成.
在破坏综合体内对野生类型和突变APC蛋白相互作用的分析.
研究关键激酶 (GSK 3β,CK1α) 的招募和β-catenin酸化状态.

主要成果:

亚辛促进了通过CRC细胞的相分离组装β-catenin破坏复杂凝聚物.
野生类型的APC稳定了这些破坏复杂的凝结物.
在CRC中常见的截断APC并没有阻碍凝析物形成,但损害了GSK3β和CK1α的招募,防止β-catenin酸化.

结论:

轴素驱动的相分离是组织β-catenin破坏复合物的关键机制.
APC突变破坏了这些凝聚物的功能完整性,导致β-catenin的积累和改变了CRC中的Wnt信号.
素的相分离能力也可能调解β-catenin的核转位,影响转录活性.

关键词:

在APC突变中出现的突变.亚克辛 (Axin) 是一种催化剂.结肠直肠癌是一种癌症.摧毁复杂的破坏综合体核运输是核运输的一种方式.阶段分离阶段分离阶段分离在Wnt/β-catenin信号通路中.

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