The catalytic activity of dsRNA-dependent protein kinase, PKR, is required for NF-kappaB activation

Oncogene
Jesús GilMariano Esteban

Abstract

The double stranded RNA-dependent protein kinase (PKR), in addition to its role as a translational controlling factor, is a key transcriptional regulator exerting antiviral and antitumoral activities. We have previously shown that induction of NF-kappaB by PKR is involved in apoptosis commitment and this process is mediated through activation of the IKK complex. To gain insights into the mechanism of activation of NF-kappaB by PKR, we have analysed the domains of PKR involved in IKK activation and subsequent NF-kappaB induction. In PKR(0/0) cells infected with a collection of vaccinia virus (VV) recombinants expressing different mutant forms of PKR, we found that only PKR forms conserving the catalytic activity are able to activate NF-kappaB. An inactive PKR mutant (K296R), was unable to induce NF-kappaB activation despite full expression of the protein in a wide range of concentrations, as defined by Western blot, EMSA, IKK kinase activity and NF-kappaB transactivation assays. Moreover, the mutant PKR (K296R) acts as a dominant negative of PKR-induced eIF-2alpha phosphorylation and NF-kappaB activation. However, PKR mutants unable to activate NF-kappaB still retain their ability to associate with the IKK complex, as confirmed ...Continue Reading

References

Mar 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D Levin, I M London
Jul 1, 1990·Virology·J F Rodriguez, G L Smith
Sep 15, 1987·European Journal of Biochemistry·A G Hovanessian, J Galabru
Nov 15, 1995·Genes & Development·I M VermaS Miyamoto
Jun 1, 1995·Trends in Biochemical Sciences·C G Proud
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E F MeursA G Hovanessian
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A KumarB R Williams
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·S B LeeM Esteban
Mar 29, 1996·The Journal of Biological Chemistry·M RoffR T Hay
Dec 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S B LeeM Esteban
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·S D DerB R Williams
Oct 23, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M J Clemens, A Elia
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
Aug 4, 1998·The EMBO Journal·R C Patel, G C Sen
May 20, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·D Rebouillat, A G Hovanessian
Sep 17, 1999·The Journal of Biological Chemistry·M Karin
Nov 26, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·C RivasM Esteban

❮ Previous
Next ❯

Citations

Feb 19, 2009·Molecular and Cellular Biochemistry·Csaba F László, Shiyong Wu
Jan 22, 2004·Viral Immunology·Sarah A Steer, John A Corbett
Sep 19, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Santanu Bose, Amiya K Banerjee
Dec 30, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Radiah A Corn MinorFarhad Imani
Jul 27, 2012·Molecular Biology of the Cell·Lucas C ReinekeRichard E Lloyd
May 4, 2004·Molecular and Cellular Biology·Jesús GilMariano Esteban
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·M A GarcíaM Esteban
Jan 28, 2014·Biochemistry. Biokhimii︠a︡·M-J DuY Cao
Oct 17, 2002·Cell Stress & Chaperones·Joshua J MalagoJaap E van Dijk
Nov 3, 2014·Annual Review of Virology·Wei-Chih Tsai, Richard E Lloyd
Apr 25, 2007·Biochimie·M A GarcíaM Esteban
Apr 5, 2013·Wiley Interdisciplinary Reviews. RNA·Richard E Lloyd
Jun 21, 2013·Chembiochem : a European Journal of Chemical Biology·Huijun BaiBertal H Aktas
Mar 17, 2010·Journal of Cellular Physiology·William L BlalockLucio Cocco
Jan 22, 2005·Seminars in Cell & Developmental Biology·Christopher G Proud
Nov 18, 2005·Pulmonary Pharmacology & Therapeutics·Michael R EdwardsSebastian L Johnston
Oct 1, 2005·Virus Research·Laura H V G GilRuben O Donis
Jan 8, 2013·Virology·Lucas C Reineke, Richard E Lloyd
Feb 3, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jesús Gil, Mariano Esteban
Jan 20, 2004·Carcinogenesis·Harris BernsteinHarinder Garewal
Jan 11, 2007·The Journal of Biological Chemistry·Helen L Eley, Michael J Tisdale
Dec 19, 2002·International Reviews of Immunology·Christopher F Basler, Adolfo García-Sastre
Aug 10, 2004·The Journal of Biological Chemistry·Xiaoling ZhangQishen Pang
Sep 27, 2019·Journal of Virology·Jane X YehDiane E Griffin
Oct 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rudolf HaaseKlaus Ruckdeschel
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A SteerJohn A Corbett
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew E GelmanLaurence A Turka
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dayna J GroskreutzGary W Hunninghake
Jun 9, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Manuela PiazziWilliam Blalock

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis