The regulation of TGF-β/SMAD signaling by protein deubiquitination

Juan Zhang; Xiaofei Zhang; Feng Xie; Zhengkui Zhang; Hans van Dam; Long Zhang; Fangfang Zhou

doi:10.1007/s13238-014-0058-8

Volume 5 Issue 7

Jul. 2014

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Article Navigation > Protein&Cell > 2014 > 5(7): 503-517

Juan Zhang, Xiaofei Zhang, Feng Xie, Zhengkui Zhang, Hans van Dam, Long Zhang, Fangfang Zhou. The regulation of TGF-β/SMAD signaling by protein deubiquitination[J]. Protein&Cell, 2014, 5(7): 503-517. doi: 10.1007/s13238-014-0058-8

Citation:

Juan Zhang, Xiaofei Zhang, Feng Xie, Zhengkui Zhang, Hans van Dam, Long Zhang, Fangfang Zhou. The regulation of TGF-β/SMAD signaling by protein deubiquitination[J]. Protein&Cell, 2014, 5(7): 503-517. doi: 10.1007/s13238-014-0058-8

Citation:

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The regulation of TGF-β/SMAD signaling by protein deubiquitination

doi: 10.1007/s13238-014-0058-8

1 Life Sciences Institute, Zhejiang University, Hangzhou 310058, China;
2 Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands and Centre of Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands

Funds:

We are grateful to all members of laboratories for discussions. We thank Prof. Dr. Peter ten Dijke for careful reading and critical comments. We would like to apologize to the authors of those papers that we could not cite due to the space limitations. This project was supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. R14C070002). This work was in part supported by Key Construction Program of the National "985" Project and Zhejiang University Special Fund for Fundamental Research, as well as the Fundamental Research Funds for the Central Universities.

Received Date: 2014-02-20
Rev Recd Date: 2014-03-28

Abstract

Abstract

Transforming growth factor-β (TGF-β) members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type Ⅱ (TβR Ⅱ) and type I (TβRI) and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes (DUBs). In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regulatory roles of these DUBs as a driving force for cancer progression as well as their underlying working mechanisms are also discussed.
- TGF-β,
- TβRI,
- SMAD,
- DUB,
- ubiquitin,
- deubiquitination