Smad6 inhibits non-canonical TGF-beta 1 signalling by recruiting the deubiquitinase A20 to TRAF6
- Authors
- Jung, Su Myung; Lee, Ji-Hyung; Park, Jinyoung; Oh, Young Sun; Lee, Sung Kyun; Park, Jin Seok; Lee, Youn Sook; Kim, Jun Hwan; Lee, Jae Young; Bae, Yoe-Sik; Koo, Seung-Hoi; Kim, Seong-Jin; Park, Seok Hee
- Issue Date
- 10월-2013
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 4
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101995
- DOI
- 10.1038/ncomms3562
- ISSN
- 2041-1723
- Abstract
- Transforming growth factor (TGF)-beta, a pivotal cytokine involved in a variety of cellular functions, transmits signals through Smad-dependent canonical and Smad-independent noncanonical pathways. In contrast to the canonical TGF-beta pathway, it is unknown how noncanonical TGF-beta pathways are negatively regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7, negatively regulates TGF-beta 1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK pathway, a noncanonical TGF-beta pathway. TGF-beta 1-induced Smad6 abolishes K63-linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38 MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of the Smad6-A20 axis in negative regulation of the TGF-beta 1-TRAF6-TAK1-p38 MAPK/JNK pathway. Therefore, our findings provide insight into the molecular mechanisms underlying negative regulation of noncanonical TGF-beta pathways.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.