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DUB3去泛素化酶通过调节ITCH、LATS和AMOT蛋白的稳定性来调控Hippo信号通路活性。

DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins.

作者信息

Nguyen Hung Thanh, Kugler Jan-Michael, Cohen Stephen M

机构信息

Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.

出版信息

PLoS One. 2017 Jan 6;12(1):e0169587. doi: 10.1371/journal.pone.0169587. eCollection 2017.

DOI:10.1371/journal.pone.0169587
PMID:28061504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5218808/
Abstract

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.

摘要

YAP和TAZ转录共激活因子可促进致癌转化。YAP/TAZ活性升高在人类肿瘤中已有记载。YAP和TAZ受Hippo肿瘤抑制通路负调控。包括YAP/TAZ在内的几种Hippo通路组分的活性和稳定性受泛素介导的蛋白质周转调控，并且几种泛素连接酶复合物与人类癌症有关。然而，对于在Hippo通路调控中抵消这些泛素连接酶的去泛素化酶知之甚少。在此，我们鉴定出DUB3家族去泛素化酶为Hippo通路活性的调节因子。我们提供的证据表明，DUB3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YAP/TAZ活性。作为一种新型的Hippo通路调节因子，DUB3有可能通过限制YAP活性发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/55e35a08f76b/pone.0169587.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/ffb083b2aca7/pone.0169587.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/052b3e0777bf/pone.0169587.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/b4a72e27d61d/pone.0169587.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/55e35a08f76b/pone.0169587.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/ffb083b2aca7/pone.0169587.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/052b3e0777bf/pone.0169587.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/b4a72e27d61d/pone.0169587.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d15/5218808/55e35a08f76b/pone.0169587.g004.jpg

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