WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway.

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-kappaB), 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-kappaB by tumor necrosis factor (TNFalpha), interleukin-1beta (IL-1beta) 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-1beta-, polyI:C- and lipopolysaccharide (LPS)-induced but not TNFalpha-induced NF-kappaB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-kappaB activation by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Humans, Interleukin-1beta, MAP Kinase Kinase Kinases, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Poly I-C, Receptors, Interleukin-1, Sequence Alignment, Signal Transduction, TNF Receptor-Associated Factor 6, Tissue Distribution, Toll-Like Receptor 3, Toll-Like Receptor 4, Two-Hybrid System Techniques
Cell. Mol. Life Sci.
Date: Aug. 01, 2009
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