Abstract
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.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects
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Cell Differentiation / drug effects
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Cytokines / physiology
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Drug Design*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Humans
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Inflammation / drug therapy
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Lymphocyte Subsets / cytology
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Lymphocyte Subsets / immunology
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Neoplasms / drug therapy
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Protein Structure, Tertiary
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / antagonists & inhibitors*
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / chemistry
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / physiology
Substances
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Cytokines
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins