A20 and A20-binding proteins as cellular inhibitors of nuclear factor-kappa B-dependent gene expression and apoptosis.
Proper gene expression and cell growth are critical for the survival of all organisms. Nuclear factor-kappa B (NF-kappa B)-dependent gene expression and apoptosis play crucial roles in numerous cellular processes, and defects in their regulation may contribute to a variety of diseases including inflammation and cancer. Although there has recently been tremendous progress in our understanding of the signaling pathways that lead to NF-kappa B activation and apoptosis, signaling mechanisms that negatively regulate these processes are only partially understood. This review deals with the zinc finger protein A20, which has been characterized as a dual inhibitor of NF-kappa B activation and apoptosis. Its inducible expression by a wide variety of stimuli, including cytokines such as tumor necrosis factor, interleukin-1, and CD40, as well as bacterial and viral products such as lipopolysaccharide, Epstein-Barr virus latent membrane protein 1, and human T-cell leukemia virus type I Tax, suggests that it is involved in the negative feedback regulation of signaling. We will discuss the possible underlying mechanisms, placing emphasis on the role of several A20-binding proteins that have recently been described. Moreover, evidence is presented that A20 and A20-binding proteins are potential novel therapeutic tools in the treatment of a variety of diseases.
Beyaert
R
R
Unit of Molecular Signal Transduction in Inflammation, Department of Molecular Biology, Ghent University, Ghent, Belgium. rudi@dmb.rug.ac.be
Heyninck
K
K
Van Huffel
S
S
D048948:14-3-3 Proteins; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047990:TNF Receptor-Associated Factor 1; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism / Q000502:physiology
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D047990:TNF Receptor-Associated Factor 1; D014446:Tyrosine 3-Monooxygenase; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3