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Cell Mol Life Sci. 2008 Oct;65(19):2964-78. doi: 10.1007/s00018-008-8064-8.

TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme.

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Department of Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.


Toll-like receptors (TLRs) as well as the receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R) play an important role in innate immunity by regulating the activity of distinct transcription factors such as nuclear factor-kappaB (NF-kappaB). TLR, IL-1R and TNF-R signaling to NF-kappaB converge on a common IkappaB kinase complex that phosphorylates the NF-kappaB inhibitory protein IkappaBalpha. However, upstream signaling components are in large part receptor-specific. Nevertheless, the principles of signaling are similar, involving the recruitment of specific adaptor proteins and the activation of kinase cascades in which protein-protein interactions are controlled by poly-ubiquitination. In this review, we will discuss our current knowledge of NF-kappaB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways.

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