TNF-receptor-associated factors as targets for drug development.
TNF-receptor-associated factors (TRAFs) are the bottleneck of the TNF-receptor (TNF-R) family signal transduction. They integrate the signalling from many members of the TNF-R family and initiate intracellular signalling cascades aimed at the activation of NF-kappaB and c-jun, the reprogramming of gene expression and the control of cell death. Deregulation of these pathways is the cause of several autoimmune and inflammatory diseases. The specificity and interaction of the members of the TRAF family with the TNF-R entails the recognition of just a 4 - 6 amino acid motif in the cytosolic region of the receptor, suitable as an attractive target for drug discovery. This review summarises the current knowledge on TRAFs and discusses the pros and cons of their application as targets for drug discovery.
Zapata
Juan M
JM
The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. jzapata@burnham.org
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000502:physiology; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology
D016207:Cytokines; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins