Molecular Steps of Tumor Necrosis Factor Receptor-Mediated Apoptosis

S.      Gupta

Abstract

Until recently it was believed that TNF-induced apoptosis is mediated exclusively by TNF-RI because TNF-RII lacks death domain. However, it has been demonstrated that TNF-RII enhances TNF-RI-mediated apoptosis. In this review, I have discussed the evidence and mechanisms by which TNF-RII regulates TNF-alpha-induced apoptosis. A role of RIP is emphasized and novel mechanisms of FLIP-mediated inhibition of apoptosis are discussed. In addition, various mechanisms of TNF-induced activation of mitochondrial pathway of apoptosis have been reviewed.

Keywords: Tumor Necrosis Factor, Receptor-Mediated Apoptosis, Tumor necrosis factor (TNF-a), TNFRI, TRADD (TNF receptor-associated death-domain), TRAF-2, MAP kinase, NFkB