Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1.
作者： Kyung-Chul Choi , Youn Sook Lee , Seunghwan Lim , Hyo Kyoung Choi , Chang-Hun Lee
DOI: 10.1038/NI1383
关键词: Signal transduction 、 Transcription factor 、 Signal transducing adaptor protein 、 Nuclear protein 、 Proinflammatory cytokine 、 Transforming growth factor beta 、 Interleukin-1 receptor 、 Interleukin-1 Receptor-Associated Kinases 、 Cancer research 、 Chemistry
摘要: Transforming growth factor-beta1 (TGF-beta1) is a potent cytokine with pleiotropic effects, including anti-inflammatory activity. Here we show that the signaling protein Smad6 bound to Pellino-1, an adaptor of mammalian interleukin 1 receptor (IL-1R)-associated kinase (IRAK1), and thereby promoted TGF-beta-mediated effects. Smad6-Pellino-1 interaction abrogated mediated by complex IRAK1, Pellino-1 TRAF6 formed after stimulation IL-1beta treatment. Blockade IRAK1-Pellino-1-TRAF6 prevented degradation inhibitor IkappaBalpha subsequent nuclear translocation transcription factor NF-kappaB thus expression proinflammatory genes. 'Knockdown' endogenous RNA interference reduced activity TGF-beta1 or TGF-beta family member BMP-4. Thus critical mediator TGF-beta-BMP pathway mediates negatively regulates IL-1R-Toll-like signals.
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