TRAF6 Mediates IL-1 beta/LPS-Induced Suppression of TGF-beta Signaling through Its Interaction with the Type III TGF-beta Receptor
- Authors
- Lim, Seunghwan; Bae, Eunjin; Kim, Hae-Suk; Kim, Tae-Aug; Byun, Kyunghee; Kim, Byungchul; Hong, Suntaek; Im, Jong Pil; Yun, Chohee; Lee, Bona; Lee, Bonghee; Park, Seok Hee; Letterio, John; Kim, Seong-Jin
- Issue Date
- 12-Mar-2012
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.7, no.3
- Journal Title
- PLOS ONE
- Volume
- 7
- Number
- 3
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16521
- DOI
- 10.1371/journal.pone.0032705
- ISSN
- 1932-6203
- Abstract
- Transforming growth factor-beta 1 (TGF-beta 1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1 beta must overcome the anti-inflammatory effects of TGF-beta to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1 beta or Lipopolysaccharide (LPS) suppresses TGF-beta-induced anti-inflammatory signaling in a NF-kappa B-independent manner. TRAF6, a key molecule in IL-1 beta signaling, mediates this suppressive effect through interaction with the type III TGF-beta receptor (T beta RIII), which is TGF-beta-dependent and requires type I TGF-beta receptor (T beta RI) kinase activity. T beta RI phosphorylates T beta RIII at residue S829, which promotes the TRAF6/T beta RIII interaction and consequent sequestration of T beta RIII from the T beta RII/T beta RI complex. Our data indicate that IL-1 beta enhances the pro-inflammatory response by suppressing TGF-beta signaling through TRAF6-mediated sequestration of T beta RIII, which may be an important contributor to the early stages of tumor progression.
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