TNF Superfamily

Recognized for their involvement in the regulation of a broad spectrum of biological processes, such as cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation, members of the Tumor Necrosis Factor (TNF) Superfamily were originally identified as necrosis-inducing, anti-tumor cytokines for their ability to cause cell death in sarcomas and other cancerous cells.  The members of the TNF Superfamily are responsible for the regulation of cellular differentiation, survival and death through the activation of multiple signal transduction pathways by ligand mediated trimerization and the resulting recruitment of several intracellular adaptors.  Although normal levels of activity can be pivotal in terms of cellular growth and regeneration, as well as regulated events of apoptosis and inflammatory response, accumulating evidence indicates that the uncontrolled synthesis of TNF Superfamily proteins can be linked to a number of human diseases and disorders of chronic inflammation, as well as autoimmune diseases, insulin resistance, and cancer.  Consequently, a great deal of interest surrounds the understanding of those pathways associated with the activity of TNF Superfamily cytokines and the development of therapeutic methods of inhibition and regulation of TNF activity, release, translation and transcription.

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