TNF-receptor-associated factors as targets for drug development

被引:34
作者
Zapata, JM [1 ]
机构
[1] Burnham Inst, La Jolla, CA 92037 USA
关键词
autoimmunity; IL-1R; jun n-terminal kinase (JNK); NF-kappa B; septic shock; toll-like receptor (TLR); TNF-R; TNF-receptor-associated factor (TRAF);
D O I
10.1517/14728222.7.3.411
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:411 / 425
页数:15
相关论文
共 126 条
[1]   The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells [J].
Ahonen, CL ;
Manning, EM ;
Erickson, LD ;
O'Connor, BP ;
Lind, EF ;
Pullen, SS ;
Kehry, MR ;
Noelle, RJ .
NATURE IMMUNOLOGY, 2002, 3 (05) :451-456
[2]   The apoptotic signaling pathway activated by Toll-like receptor-2 [J].
Aliprantis, AO ;
Yang, RB ;
Weiss, DS ;
Godowski, P ;
Zychlinsky, A .
EMBO JOURNAL, 2000, 19 (13) :3325-3336
[3]   A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function [J].
Armstrong, AP ;
Tometsko, ME ;
Glaccum, M ;
Sutherland, CL ;
Cosman, D ;
Dougall, WC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (46) :44347-44356
[4]   Regulation of the subcellular localization of tumor necrosis factor receptor-associated factor (TRAF)2 by TRAF1 reveals mechanisms of TRAF2 signaling [J].
Arron, JR ;
Pewzner-Jung, Y ;
Walsh, MC ;
Kobayashi, T ;
Choi, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (07) :923-934
[5]   Apoptosis control by death and decoy receptors [J].
Ashkenazi, A ;
Dixit, VM .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (02) :255-260
[6]   Signal transduction by tumor necrosis factor and its relatives [J].
Baud, V ;
Karin, M .
TRENDS IN CELL BIOLOGY, 2001, 11 (09) :372-377
[7]   The molecular architecture of the TNF superfamily [J].
Bodmer, JL ;
Schneider, P ;
Tschopp, J .
TRENDS IN BIOCHEMICAL SCIENCES, 2002, 27 (01) :19-26
[8]   Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily [J].
Boucher, LM ;
Marengere, LEM ;
Lu, Y ;
Thukral, S ;
Mak, TW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 233 (03) :592-600
[9]   Tumor necrosis factor receptor-associated factors (TRAFs) [J].
Bradley, JR ;
Pober, JS .
ONCOGENE, 2001, 20 (44) :6482-6491
[10]   Tumor necrosis factor receptor (TNFR)-associated factor 2A (TRAF2A), a TRAF2 splice variant with an extended RING finger domain that inhibits TNFR2-mediated NF-κB activation [J].
Brink, R ;
Lodish, HF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (07) :4129-4134