The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity

• Published in: The Journal of biological chemistry Vol. 267; no. 18; pp. 12424 - 12427
• Main Authors: A W Opipari, Jr, H M Hu, R Yabkowitz, V M Dixit
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-06-1992
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Cell Death; Cell Line; Cell physiology; Cytotoxicity, Immunologic; Endothelium, Vascular - immunology; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Mice; Molecular and cellular biology; Precipitin Tests; Responses to growth factors, tumor promotors, other factors; Transfection; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - physiology; Zinc Fingers - physiology; Human; Tumor necrosis factor; Induction; Zinc finger structure; Cytotoxicity; Tumor; Gene expression
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)42292-2

Resistance against the cytotoxic actions of tumor necrosis factor alpha (TNF) is an active process requiring the synthesis
of TNF-inducible proteins. The specific TNF-induced proteins so far identified (manganese superoxide dismutase and plasminogen
activator inhibitor type 2) as having a role in resistance against TNF cytotoxicity are able to confer only partial protection
to cells, suggesting that other genes are involved. A20 is a TNF-induced primary response gene which encodes a novel zinc
finger protein. In this report we demonstrate that A20 protein is induced by TNF in a variety of cells. A survey of A20 expression
in human breast carcinoma cell lines that are either sensitive or resistant to TNF cytotoxicity revealed increased expression
of A20 message and protein in TNF-resistant cells. Constitutive expression of A20 after stable transfection of NIH 3T3 and
WEHI 164 cells results in significant, but partial, resistance to TNF cytotoxicity. This work gives additional support to
a role for TNF-induced immediate early response genes in protecting cells from TNF-induced death.