The regulation of TGF-β/SMAD signaling by protein deubiquitination.
10.1007/s13238-014-0058-8
- Author:
Juan ZHANG
1
;
Xiaofei ZHANG
;
Feng XIE
;
Zhengkui ZHANG
;
Hans VAN DAM
;
Long ZHANG
;
Fangfang ZHOU
Author Information
1. Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Humans;
Molecular Targeted Therapy;
Receptors, Transforming Growth Factor beta;
metabolism;
Signal Transduction;
Smad Proteins;
physiology;
Transforming Growth Factor beta;
physiology;
Ubiquitin Thiolesterase;
metabolism;
Ubiquitin-Specific Proteases;
Ubiquitination
- From:
Protein & Cell
2014;5(7):503-517
- CountryChina
- Language:English
-
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.
