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TRAF Family Proteins Link PKR with NF-κB Activation

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dc.contributor European Commission
dc.contributor Fundación Ramón Areces
dc.contributor Human Frontier Science Program
dc.contributor Ministerio de Ciencia y Tecnología (España)
dc.creator Gil, Jesús
dc.creator García-Chaves, María Ángel
dc.creator Gómez-Puertas, Paulino
dc.creator Guerra, Susana
dc.creator Rullas, Joaquín
dc.creator Nakano, Hiroyasu
dc.creator Alcamí, José
dc.creator Esteban, Mariano
dc.date 2008-06-13T07:08:05Z
dc.date 2008-06-13T07:08:05Z
dc.date 2004-05
dc.date.accessioned 2017-01-31T01:40:37Z
dc.date.available 2017-01-31T01:40:37Z
dc.identifier Molecular and Cellular Biology 24(10): 4502-4512 (2004)
dc.identifier 1098-5549
dc.identifier 0270-7306
dc.identifier http://hdl.handle.net/10261/5054
dc.identifier 10.1128/MCB.24.10.4502-4512.2004
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5054
dc.description 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.
dc.description This investigation was supported by research grants BMC2002- 03246 and BIO2000-0340-P4 from Spain and QLK2-CT2002-00954 from the European Union to M.E., by grants SAF2000-0028 and FIPSE to J.A., and by the Fundación Ramón Areces (P.G.-P.). H.N. is supported by a grant from the Human Frontier Science Program. M.A.G. and J.G. were supported by fellowships from the Ministerio de Ciencia y Tecnología, Madrid, Spain.
dc.description Peer reviewed
dc.format 25043 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Microbiology
dc.relation http://dx.doi.org/10.1128/MCB.24.10.4502-4512.2004
dc.rights closedAccess
dc.title TRAF Family Proteins Link PKR with NF-κB Activation
dc.type Artículo

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