2. Academic Validation
  3. Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie

Usp7 regulates Hippo pathway through deubiquitinating the transcriptional coactivator Yorkie

  • Nat Commun. 2019 Jan 24;10(1):411. doi: 10.1038/s41467-019-08334-7.
Xiaohan Sun 1,  Yan Ding 1,  Meixiao Zhan 2,  Yan Li 1,  Dongqing Gao 1,  Guiping Wang 3,  Yang Gao 3,  Yong Li 2,  Shian Wu 3,  Ligong Lu 4,  Qingxin Liu 5,  Zizhang Zhou 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.
  • 2 Center of Intervention radiology, Zhuhai Precision Medicine Center, Zhuhai People's Hospital, 519000, Zhuhai, China.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 300071, Tianjin, China.
  • 4 Center of Intervention radiology, Zhuhai Precision Medicine Center, Zhuhai People's Hospital, 519000, Zhuhai, China. luligong1969@126.com.
  • 5 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China. liuqingxin@sdau.edu.cn.
  • 6 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China. zhouzz@sdau.edu.cn.
PMID: 30679505 DOI: 10.1038/s41467-019-08334-7
Abstract

The Hippo pathway plays an important role in organ development and adult tissue homeostasis, and its deregulation has been implicated in many cancers. The Hippo signaling relies on a core kinase cascade culminating in phosphorylation of the transcription coactivator Yorkie (Yki). Although Yki is the key effector of Hippo pathway, the regulation of its protein stability is still unclear. Here, we show that Hippo pathway attenuates the binding of a Ubiquitin-Specific Protease Usp7 to Yki, which regulates Hippo signaling through deubiquitinating Yki. Furthermore, the mammalian homolog of USP7, HAUSP plays a conserved role in regulating Hippo pathway by modulating YAP ubiquitination and degradation. Finally, we find that the expression of HAUSP is positively correlated with that of YAP, both showing upregulated levels in clinical hepatocellular carcinoma (HCC) specimens. In summary, our findings demonstrate that Yki/YAP is stabilized by USP7/HAUSP, and provide HAUSP as a potential therapeutic target for HCC.

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