Targeting TRAfs for therapeutic intervention.
TNF-receptor associated factors (TRAFs) are the molecules that upon engagement of the TNF-receptor (TNFR) by a TNF-family ligand come first in contact with the activated TNFR, initially acting as docking molecules for kinases and other effector proteins that are recruited to the activated receptor. TRAFs later regulate the subcellular relocalization of the receptor-ligand complex and finally they modulate the extent of the response by controlling the degradation of key proteins in the pathway. In this chapter, we review the involvement of different TRAF family members in the etiology of a variety of pathologies and address the question of whether the use of TNFR-mimic-peptides or small molecule modulators targeting TRAFs might be suitable for therapeutic intervention, discussing the advantages and disadvantages of this strategy.
Zapata
Juan M
JM
Burnham Institute for Medical Research, La Jolla, California 92037, USA. jzapata@burnham.org
Lefebvre
Sophie
S
Reed
John C
JC
D000818:Animals; D003141:Communicable Diseases / Q000188:drug therapy / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins