Positive and negative signaling components involved in TNF alpha-induced NF-kappa B activation

Tumor Necrosis Factor alpha (TNF alpha) 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 TNF alpha is the NF-kappa B transcription factor, which has been identified to be involved in inflammatory, anti-apoptotic, and immune responses. Stimulation of cells with TNF alpha triggers activation of NF-kappa B 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-kappa B is activated upon TNF alpha 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. (c) 2007 Elsevier Ltd. All rights reserved.