A20 inhibits NF-kappaB activation by dual ubiquitin-editing functions.
Deregulation of the transcription factor NF-kappaB can mediate several inflammatory diseases in addition to cancer. Therefore, several proteins, including the zinc finger protein A20, tightly control its activation. Recently, the underlying mechanism by which A20 downregulates NF-kappaB activation in response to the pro-inflammatory cytokine tumor necrosis factor (TNF) has been described. A20 was shown to exert two opposing activities: sequential de-ubiquitination and ubiquitination of the TNF receptor-interacting protein (RIP), thereby targeting RIP to proteasomal degradation.
Heyninck
Karen
K
Department of Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Ghent University - VIB, Technologiepark 927, B-9052 Zwijnaarde, Belgium.
Beyaert
Rudi
R
D000818:Animals; D004268:DNA-Binding Proteins; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D048069:Tumor Necrosis Factors / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D048069:Tumor Necrosis Factors; D025801:Ubiquitin; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D046988:Proteasome Endopeptidase Complex