TRAF Family Proteins Link PKR with NF-κB Activation

• DOI: 10.1128/mcb.24.10.4502-4512.2004
• Publication Date: 2004-04-30T19:27:56Z
• Authors: Jesús Gil; Maria Angel García; Paulino Gomez-Pue...; Susana Guerra; Joaquín Rullas; Hiroyasu Nakano; José Alcamí; Mariano Esteban
• Keywords: Protein kinase R; EIF-2 kinase; Immunoprecipitation; Sequence motif

The double-stranded RNA (dsRNA)-dependent protein kinase PKR activates NF-κB via the IκB (IKK) complex, but little is known about additional molecules that may be involved in this pathway. Analysis of sequence enabled us to identify two putative TRAF-interacting motifs. viability such an interaction was further suggested by computer modeling. Here, we present evidence colocalization and physical between TRAF family proteins vivo, as shown immunoprecipitation confocal microscopy experiments. This induced upon dimerization. Most importantly, show binding TRAFs functionally relevant, observed absence activity expression cells genetically deficient TRAF2 TRAF5 or after dominant negative molecules. On basis information mutational docking analyses, favored a TRAF-PKR model which C-terminal domain binds predicted motif domain. Altogether, our data suggest are key components located downstream have important role mediating activation dsRNA-dependent kinase.