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Free Radic Biol Med. 1998 Jul 1;25(1):57-65.

TNF-induced mitochondrial changes and activation of apoptotic proteases are inhibited by A20.

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1
Apoptosis Laboratory, Institute of Cancer Biology, Danish Cancer Society, Copenhagen.

Abstract

A20 zinc finger protein is a product of a cytokine-induced primary response gene. It functions as a negative regulator of the tumor necrosis factor (TNF) inhibiting both TNF-mediated apoptosis and activation of transcription factors. We demonstrated that A20 overexpression blocks early TNF-induced signaling events including the generation of free radicals, the fall in mitochondrial transmembrane potential (delta psi(m)), and the activation of caspase-3-like apoptotic proteases. General inhibitor of caspases, cow pox virus-derived CrmA, also inhibited TNF-induced mitochondrial changes indicating that early caspase activation occurs upstream from mitochondrial changes. Interestingly, changes in mitochondrial function or induction of caspase-3-like activity induced by anti-Fas or doxorubicin were not inhibited by A20. The data show that A20 is a specific inhibitor of TNF signaling and acts upstream of INF-induced free radical formation, fall in mitochondrial transmembrane potential (delta psi(m)), and activation of caspase-3-like proteases.

PMID:
9655522
[Indexed for MEDLINE]
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