PDZ域
河马信号通路
细胞生物学
WW域
效应器
生物
核定位序列
核心
支架蛋白
核蛋白
抑制器
磷酸化
信号转导
激活剂(遗传学)
细胞凋亡
转录因子
生物化学
基因
作者
Tsutomu Oka,Eline Remue,Kris Meerschaert,Berlinda Vanloo,Ciska Boucherie,David Gfeller,Gary D. Bader,Sachdev S. Sidhu,Joël Vandekerckhove,Jan Gettemans,Marius Sudol
摘要
The Hippo pathway regulates the size of organs by controlling two opposing processes: proliferation and apoptosis. YAP2 (Yes kinase-associated protein 2), one of the three isoforms of YAP, is a WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells. In addition to WW domains, YAP2 has a PDZ-binding motif at its C-terminus. We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2 and YAP2 proteins co-localize in the nucleus. We also found that ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2, and that this activity of ZO-2 is PDZ-domain-dependent. The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2–ZO-2 complex could represent a target for cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI