期刊
BIOCHEMICAL JOURNAL
卷 432, 期 -, 页码 461-472出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20100870
关键词
Hippo pathway; nuclear translocation; PDZ domain; Yes kinase-associated protein 2 (YAP2); zona occludens protein
资金
- PA Department of Health and Breast Cancer Coalition
- Geisinger Clinic [RFA60707, RFA9200903]
- Canadian Institute of Health Research [MOP-84324]
- Swiss National Science Foundation [PBELA-120936]
- research council of Ghent University (BOF)
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.
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