| Title | WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappa B activation pathway |
| Authors | Gao, Dong Wang, Ruipeng Li, Bingfeng Yang, Yongkang Zhai, Zhonghe Chen, Dan-Ying |
| Affiliation | Peking Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China. |
| Keywords | TAK1 WDR34 IL-1R TLR4 TLR3 NF-kappa B BETA SIGNAL-TRANSDUCTION INNATE IMMUNE-RESPONSES KINASE KINASE KINASE TAK1 MAPKKK TAK1-BINDING PROTEIN-1 CRITICAL ROLES TAB1 IL-1 DROSOPHILA BINDING |
| Issue Date | 2009 |
| Publisher | cellular and molecular life sciences |
| Citation | CELLULAR AND MOLECULAR LIFE SCIENCES.2009,66,(15),2573-2584. |
| Abstract | Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways activate the nuclear factor-kappaB (NF-kappa B), which controls the expression of inflammatory cytokine genes. Transforming growth factor-beta-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-kappa B by tumor necrosis factor (TNF alpha), interleukin-1 beta (IL-1 beta) and TLR ligands. In this study, we identified a novel protein, WD40 domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression and under physiological conditions. Overexpression of WDR34 inhibited IL-1 beta-, polyI:C- and lipopolysaccharide (LPS)-induced but not TNF alpha-induced NF-kappa B activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-kappa B activation by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-kappa B activation pathway. |
| URI | http://hdl.handle.net/20.500.11897/319987 |
| ISSN | 1420-682X |
| DOI | 10.1007/s00018-009-0059-6 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 |
