Open AccessFailure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Author(s) -
Eric G. Lee,
David L. Boone,
Sophia Chai,
Shon Libby,
Marcia Chien,
James P. Lodolce,
Averil Ma
Publication year - 2000
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.289.5488.2350
Subject(s) - tumor necrosis factor alpha , inflammation , programmed cell death , nfkb1 , lipopolysaccharide , microbiology and biotechnology , biology , in vivo , apoptosis , nf κb , cancer research , chemistry , immunology , transcription factor , biochemistry , gene
A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF-kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappaB responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo.