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Cytokine. 2008 Jan;41(1):1-8.

Positive and negative signaling components involved in TNFalpha-induced NF-kappaB activation.

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Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 108, Houston, TX 77030, USA.


Tumor Necrosis Factor alpha (TNFalpha) is a pro-inflammatory cytokine that plays important roles in different biological processes, including the induction of other cytokines. One of the most important downstream signaling targets activated by TNFalpha is the NF-kappaB transcription factor, which has been identified to be involved in inflammatory, anti-apoptotic, and immune responses. Stimulation of cells with TNFalpha triggers activation of NF-kappaB through various signaling molecules, including TRAF2, RIP, MAP3K, and the IKK complex. Recently, numerous studies have been performed to explore the detailed mechanism by which NF-kappaB is activated upon TNFalpha stimulation. Current understanding of this pathway has been focused on the identification of signaling components, the role of post-translational modification and the sub-cellular translocation of those components. Additionally, more negative regulators in the TNF-IKK pathway are emerging.

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