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

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Protein Cell ›› 2014, Vol. 5 ›› Issue (7) : 503-517. DOI: 10.1007/s13238-014-0058-8
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The regulation of TGF-β/SMAD signaling by protein deubiquitination

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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.

Keywords

TGF-β / TβRI / SMAD / DUB / ubiquitin / deubiquitination

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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. Protein Cell, 2014, 5(7): 503‒517 https://doi.org/10.1007/s13238-014-0058-8

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