Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UK.
Cells. 2021 Feb 23;10(2):478. doi: 10.3390/cells10020478.
The Hippo pathway regulates a complex signalling network which mediates several biological functions including cell proliferation, organ size and apoptosis. Several scaffold proteins regulate the crosstalk of the members of the pathway with other signalling pathways and play an important role in the diverse output controlled by this pathway. In this study we have identified the scaffold protein IQGAP1 as a novel interactor of the core kinases of the Hippo pathway, MST2 and LATS1. Our results indicate that IQGAP1 scaffolds MST2 and LATS1 supresses their kinase activity and YAP1-dependent transcription. Additionally, we show that IQGAP1 is a negative regulator of the non-canonical pro-apoptotic pathway and may enable the crosstalk between this pathway and the ERK and AKT signalling modules. Our data also show that bile acids regulate the IQGAP1-MST2-LATS1 signalling module in hepatocellular carcinoma cells, which could be necessary for the inhibition of MST2-dependent apoptosis and hepatocyte transformation.
Hippo 通路调节着一个复杂的信号网络，介导包括细胞增殖、器官大小和细胞凋亡在内的多种生物学功能。几种支架蛋白调节该通路成员与其他信号通路的串扰，并在该通路控制的多种输出中发挥重要作用。在这项研究中，我们鉴定了支架蛋白 IQGAP1 作为 Hippo 通路核心激酶 MST2 和 LATS1 的一个新的相互作用蛋白。我们的结果表明，IQGAP1 支架 MST2 和 LATS1 抑制它们的激酶活性和 YAP1 依赖性转录。此外，我们表明 IQGAP1 是一种非经典促凋亡途径的负调节剂，并且可能使该途径与 ERK 和 AKT 信号模块之间发生串扰。我们的数据还表明，胆酸调节肝癌细胞中的 IQGAP1-MST2-LATS1 信号模块，这对于抑制 MST2 依赖性细胞凋亡和肝细胞转化可能是必需的。
