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The FASEB Journal, Vol 4, 3215-3223, Copyright © 1990 by The Federation of American Societies for Experimental Biology

REVIEWS

Cytotoxic mechanism of tumor necrosis factor-alpha

JW Larrick and SC Wright
Genelabs Incorporated, Redwood City, California 94063.

Many intracellular pathways are set in motion by the binding of tumor necrosis factor (TNF) to its cell surface receptor. Major steps in the TNF-mediated cytotoxicity cascade include G protein-coupled activation of phospholipases, generation of free radicals, and damage to nuclear DNA by endonucleases. Ultimately the cells undergo apoptosis and die. Understanding how TNF initiates these pathways will facilitate the rational design of pharmaceuticals that can attenuate or potentiate the action of this important cytokine.


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