The regulation of TGF-β/SMAD signaling by protein deubiquitination. Issue 7 (23rd April 2014)

• Record Type: Journal Article
• Authors: Zhang, Juan; Zhang, Xiaofei; Xie, Feng; Zhang, Zhengkui; van Dam, Hans; Zhang, Long; Zhou, Fangfang
• Is Part Of: Protein & cell. Volume 5:Issue 7(2014)
• Page Start: 503
• Page End: 517
• Publication Date: 2014-04-23
• Subjects: TGF-β -- TβRI -- SMAD -- DUB -- ubiquitin -- deubiquitination; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-014-0058-8
• Languages: English
• ISSNs: 1674-800X

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.