Sixian Qi, Yuwen Zhu, Xincheng Liu, Pengyue Li, Yebin Wang, Yan Zeng, Aijuan Yu, Yu Wang, Zhao Sha, Zhenxing Zhong, Rui Zhu, Haixin Yuan, Dan Ye, Shenglin Huang, Chen Ling, Yanhui Xu, Dawang Zhou, Lei Zhang, Fa-Xing Yu
YAP and TAZ (YAP/TAZ), two major effectors of the Hippo signaling pathway, are frequently activated in human cancers. The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. However, it is unclear how LATS1/2 are precisely regulated by upstream factors such as Hippo kinases MST1/2. Here, we show that WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. Hence, WWC1/2/3 play an organizer role in a signaling module that mediates LATS1/2 activation by MST1/2...
May 19, 2022: Molecular Cell