1.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
Protein & Cell 2014;5(7):503-517
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.
Animals
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Humans
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Molecular Targeted Therapy
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Receptors, Transforming Growth Factor beta
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metabolism
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Signal Transduction
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Smad Proteins
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physiology
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Transforming Growth Factor beta
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physiology
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Ubiquitin Thiolesterase
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metabolism
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Ubiquitin-Specific Proteases
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Ubiquitination