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Itch E3 Ubiquitin Ligase Positively Regulates TGF-beta Signaling to EMT via Smad7 Ubiquitination

Title
Itch E3 Ubiquitin Ligase Positively Regulates TGF-beta Signaling to EMT via Smad7 Ubiquitination
Authors
Park, Su-hyunJung, Eun-HoKim, Geun-YoungKim, Byung-ChulLim, Jae HyangWoo, Chang-Hoon
Ewha Authors
임재향
SCOPUS Author ID
임재향scopus
Issue Date
2015
Journal Title
MOLECULES AND CELLS
ISSN
1016-8478JCR Link0219-1032JCR Link
Citation
vol. 38, no. 1, pp. 20 - 25
Keywords
EMTItchSmad7TGF-betaubiquitination
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Indexed
SCI; SCIE; SCOPUS; KCI WOS
Abstract
TGF-beta regulates pleiotropic cellular responses including cell growth, differentiation, migration, apoptosis, extracellular matrix production, and many other biological processes. Although non-Smad signaling pathways are being increasingly reported to play many roles in TGF-beta-mediated biological processes, Smads, especially receptor-regulated Smads (R-Smads), still play a central mediatory role in TGF-beta signaling for epithelial-mesenchymal transition. Thus, the biological activities of R-Smads are tightly regulated at multiple points. Inhibitory Smad (I-Smad also called Smad7) acts as a critical endogenous negative feedback regulator of Smad-signaling pathways by inhibiting R-Smad phosphorylation and by inducing activated type I TGF-beta receptor degradation. Roles played by Smad7 in health and disease are being increasingly reported, but the molecular mechanisms that regulate Smad7 are not well understood. In this study, we show that E3 ubiquitin ligase Itch acts as a positive regulator of TGF-beta signaling and of subsequent EMT-related gene expression. Interestingly, the Itch-mediated positive regulation of TGF-beta signaling was found to be dependent on Smad7 ubiquitination and its subsequent degradation. Further study revealed Itch acts as an E3 ubiquitin ligase for Smad7 polyubiquitination, and thus, that Itch is an important regulator of Smad7 activity and a positive regulator of TGF-beta signaling and of TGF-beta-mediated biological processes. Accordingly, the study uncovers a novel regulatory mechanism whereby Smad7 is controlled by Itch.
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의학전문대학원 > 의학과 > Journal papers
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