title: The regulation of TGF-β/SMAD signaling by protein deubiquitination.
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.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: Zhengkui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hans
authors.initials: H
authors.lastname: van Dam
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C486203:USP4 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases
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