河马信号通路
泛素连接酶
细胞生物学
效应器
生物
癌症研究
泛素
遗传学
基因
作者
Wenqi Wang,Nan Li,Xu Li,My Kim Tran,Xin Han,Junjie Chen
出处
期刊:Cell Reports
[Elsevier]
日期:2015-10-01
卷期号:13 (3): 524-532
被引量:162
标识
DOI:10.1016/j.celrep.2015.09.014
摘要
Summary
As the key effector in the Hippo pathway, YAP was identified as an oncoprotein whose expression is elevated in various human cancers. However, the development of potentially therapeutic compounds targeting YAP has been slow and limited. Here, we find that tankyrase inhibitors suppress YAP activity. This effect is mediated by anigomotin (AMOT) family proteins. Tankyrases associate with AMOT family proteins and promote their degradation through E3 ligase RNF146. By antagonizing tankyrase activity, tankyrase inhibitors stabilize AMOT family proteins, thereby suppressing YAP oncogenic functions. Together, our studies not only demonstrate the tankyrase-RNF146-AMOT axis as an upstream pathway regulating YAP but also reveal a therapeutic opportunity in targeting YAP for cancer treatment.
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