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Closed Access item TRAF Family Proteins Link PKR with NF-κB Activation

Authors:Gil, Jesús
García-Chaves, María Ángel
Gómez-Puertas, Paulino
Guerra, Susana
Rullas, Joaquín
Nakano, Hiroyasu
Alcamí, José
Esteban, Mariano
Issue Date:May-2004
Publisher:American Society for Microbiology
Citation:Molecular and Cellular Biology 24(10): 4502-4512 (2004)
Abstract:The double-stranded RNA (dsRNA)-dependent protein kinase PKR activates NF-κB via the IκB kinase (IKK) complex, but little is known about additional molecules that may be involved in this pathway. Analysis of the PKR sequence enabled us to identify two putative TRAF-interacting motifs. The viability of such an interaction was further suggested by computer modeling. Here, we present evidence of the colocalization and physical interaction between PKR and TRAF family proteins in vivo, as shown by immunoprecipitation and confocal microscopy experiments. This interaction is induced upon PKR dimerization. Most importantly, we show that the binding between PKR and TRAFs is functionally relevant, as observed by the absence of NF-κB activity upon PKR expression in cells genetically deficient in TRAF2 and TRAF5 or after expression of TRAF dominant negative molecules. On the basis of sequence information and mutational and computer docking analyses, we favored a TRAF-PKR interaction model in which the C-terminal domain of TRAF binds to a predicted TRAF interaction motif present in the PKR kinase domain. Altogether, our data suggest that TRAF family proteins are key components located downstream of PKR that have an important role in mediating activation of NF-κB by the dsRNA-dependent protein kinase.
Publisher version (URL):http://dx.doi.org/10.1128/MCB.24.10.4502-4512.2004
URI:http://hdl.handle.net/10261/5054
ISSN:1098-5549
0270-7306
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