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Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB

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Kumar_et_al._1997.pdf
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1997

Autor:innen

Kumar, Aseem
Yang, Yi-Li
Flati, Vincenzo
Der, Sandy
Deb, Amitabha
Haque, Jaharul
Reis, Luiz
Weissmann, Charles
Williams, Bryan R. G.

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Published

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EMBO Journal. 1997, 16(2), pp. 406-416. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1093/emboj/16.2.406

Zusammenfassung

The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated Ser/Thr protein kinase (PKR) plays a role in the antiviral and antiproliferative effects of IFN. PKR phosphorylates initiation factor eIF2alpha, thereby inhibiting protein synthesis, and also activates the transcription factor, nuclear factor-kappaB (NF-kappaB), by phosphorylating the inhibitor of NF-kappaB, IkappaB. Mice devoid of functional PKR (Pkr(o/o)) derived by targeted gene disruption exhibit a diminished response to IFN-gamma and poly(rI:rC) (pIC). In embryo fibroblasts derived from Pkr(o/o) mice, interferon regulatory factor 1 (IRF-1) or guanylate binding protein (Gbp) promoter-reporter constructs were unresponsive to IFN-gamma or pIC but response could be restored by co-transfection with PKR. The lack of responsiveness could be attributed to a diminished activation of IRF-1 and/or NF-kappaB in response to IFN-gamma or pIC. Thus, PKR acts as a signal transducer for IFN-stimulated genes dependent on the transcription factors IRF-1 and NF-kappaB.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

cytokine signaling, interferon, IRF-1, NF-kB, PKR gene

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ISO 690KUMAR, Aseem, Yi-Li YANG, Vincenzo FLATI, Sandy DER, Suzanne KADEREIT, Amitabha DEB, Jaharul HAQUE, Luiz REIS, Charles WEISSMANN, Bryan R. G. WILLIAMS, 1997. Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB. In: EMBO Journal. 1997, 16(2), pp. 406-416. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1093/emboj/16.2.406
BibTex
@article{Kumar1997Defic-8063,
  year={1997},
  doi={10.1093/emboj/16.2.406},
  title={Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB},
  number={2},
  volume={16},
  issn={0261-4189},
  journal={EMBO Journal},
  pages={406--416},
  author={Kumar, Aseem and Yang, Yi-Li and Flati, Vincenzo and Der, Sandy and Kadereit, Suzanne and Deb, Amitabha and Haque, Jaharul and Reis, Luiz and Weissmann, Charles and Williams, Bryan R. G.}
}
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