DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins.
DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins.
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DOI：
10.1371/journal.pone.0169587
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Cohen SM
中科院分区：
文献类型：
--
作者：
Nguyen HT;Kugler JM;Cohen SM
雅普和TAZ转录共激活因子促进致癌转化。在人类肿瘤中已经记录了升高的雅普/TAZ活性。雅普和TAZ受Hippo肿瘤抑制途径负调控。包括雅普/TAZ在内的几种Hippo途径组分的活性和稳定性受泛素介导的蛋白质周转调节，并且几种泛素连接酶复合物与人类癌症有关。然而，鲜为人知的是去泛素化酶，抵消这些泛素连接酶的调节河马途径。在这里，我们确定DUB 3家族去泛素化酶作为Hippo通路活性的调节剂。我们提供的证据表明DUB 3蛋白通过控制E3连接酶ITCH、LATS激酶和AMOT家族蛋白的稳定性来调节雅普/TAZ活性。DUB 3作为一种新的Hippo信号通路调节因子，具有通过限制雅普活性而发挥肿瘤抑制作用的潜力。
The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor by limiting YAP activity.
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DOI：
10.1126/science.1194472
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harbour JW;Onken MD;Roberson ED;Duan S;Cao L;Worley LA;Council ML;Matatall KA;Helms C;Bowcock AM
通讯作者：
Bowcock AM
影响因子：
4.8
作者：
Mouchantaf, Rania;Azakir, Bilal A.;Angers, Annie
通讯作者：
Angers, Annie
影响因子：
64.5
作者：
Kapoor A;Yao W;Ying H;Hua S;Liewen A;Wang Q;Zhong Y;Wu CJ;Sadanandam A;Hu B;Chang Q;Chu GC;Al-Khalil R;Jiang S;Xia H;Fletcher-Sananikone E;Lim C;Horwitz GI;Viale A;Pettazzoni P;Sanchez N;Wang H;Protopopov A;Zhang J;Heffernan T;Johnson RL;Chin L;Wang YA;Draetta G;DePinho RA
通讯作者：
DePinho RA
影响因子：
16.6
作者：
Bae, Sung Jun;Kim, Myungjin;Seol, Jae Hong
通讯作者：
Seol, Jae Hong
DOI：
10.1073/pnas.1101273108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Ho, King Ching;Zhou, Zhonghua;Yang, Xiaolong
通讯作者：
Yang, Xiaolong