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Transcriptional Regulation

PKR Stimulates NF-κB Irrespective of Its Kinase Function by Interacting with the IκB Kinase Complex

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Pages 4532-4542 | Received 11 Feb 2000, Accepted 27 Mar 2000, Published online: 28 Mar 2023

REFERENCES

  • Alkalay, I., Yaron, A., Hatzubai, A., Orian, A., Ciechanover, A., and Ben-Neriah, Y.. 1995. Stimulation-dependent IκB phosphorylation marks the NF-κB inhibitor for degradation via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 92:10599–10603
  • Baeuerle, P., and Baichwal, V.. 1997. NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol. 65:111–136
  • Baldwin, A.. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14:649–681
  • Benkirane, M., Neuveut, C., Chun, R. F., Smith, S. M., Samuel, C. E., Gatignol, A., and Jeang, K.-T.. 1997. Oncogenic potential of TAR RNA-binding TRBP and its regulatory interaction with protein kinase R. EMBO J. 16:611–624
  • Berlanga, J. J., Santoyo, J., and De Haro, C.. 1999. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2α kinase. Eur. J. Biochem. 265:754–762
  • Berlanga, J. J., Herrero, S., and De Haro, C.. 1998. Characterization of the hemin-sensitive eukaryotic initiation factor 2α kinase from mouse nonerythroid cells. J. Biol. Chem. 273:32340–32346
  • Chen, Z., Hagler, J., Palombella, V., Melandri, F., Scherer, D., Ballard, D., and Maniatis, T.. 1995. Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev. 9:1586–1597
  • Chong, K., Feng, L., Donahue, T. F., Friesen, J. D., Meurs, E., Hovanessian, A. G., and Williams, B. R. G.. 1992. Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J. 11:1553–1562
  • Chu, W. M., Ostertag, D., Li, Z., Chang, L., Chen, Y., Hu, Y., Williams, B. R. G., Perrault, J., and Karin, M.. 1999. JNK2 and IKKβ are required for activating the innate response to viral infection. Immunity 11:721–731
  • Clemens, M. J., and Androulla, E.. 1997. The double-stranded RNA-dependent protein kinase PKR: structure and function. J. Interferon Res. 17:503–524
  • Clemens, M. J., and Bommer, U. A.. 1999. Translational control: the cancer connection. Int. J. Biochem. Cell Biol. 31:1–23
  • Courtois, G., Whiteside, S. T., Sibley, C. H., and Israel, A.. 1997. Characterization of a mutant cell line that does not activate NF-κB in response to multiple stimuli. Mol. Cell. Biol. 17:1441–1449
  • Craig, A., Cosentino, G., Donze, O., and Sonenberg, N.. 1996. The kinase insert domain of interferon-induced protein kinase PKR is required for activity but not for interaction with the pseudosubstrate K3L. J. Biol. Chem. 271:24526–24533
  • Dever, T. E., Chen, J. J., Barber, G. N., Cigan, A. M., Feng, L., Donahue, T. F., London, I. M., Katze, M. G., and Hinnebusch, A. G.. 1993. Mammalian eIF-2α kinases functionally substitute for GCN2 and stimulate GCN4 translation in yeast. Proc. Natl. Acad. Sci. USA 90:4616–4620
  • DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., and Karin, M.. 1997. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388:548–554
  • Duh, E. J., Maury, W. J., Folks, T. M., Fauci, A. S., and Rabson, A. B.. 1989. Tumor necrosis factor α activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-κB sites in the long terminal repeat. Proc. Natl. Acad. Sci. USA 86:5974–5978
  • Everett, H., and McFadden, G.. 1999. Apoptosis: an innate immune response to virus infection. Trends Microbiol. 7:160–165
  • Gil, J., Alcami, J., and Esteban, M.. 1999. Induction of apoptosis by double-stranded-RNA-dependent protein kinase (PKR) involves the α subunit of eukaryotic translation initiation factor 2 and NF-κB. Mol. Cell. Biol. 19:4653–4663
  • Harding, H. P., Zhang, Y., and Ron, D.. 1999. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397:271–274
  • Henkel, T., Zabel, U., Van Zee, K., Muller, J., Fanning, E., and Baeuerle, P. A.. 1992. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-κB subunit. Cell 68:1121–1133
  • Hershey, J. W.. 1991. Translational control in mammalian cells. Annu. Rev. Biochem. 60:717–755
  • Hovanessian, A. G.. 1989. The double-stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. J. Interferon Res. 9:641–647
  • Hsu, H., Huang, J., Shu, H.-B., Baichwal, V., and Goeddel, D. V.. 1996. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4:387–396
  • Hu, Y., Baud, V., Delhase, M., Zhang, P., Deerinck, T., Ellisman, M., Johnson, R., and Karin, M.. 1999. Abnormal morphogenesis but intact IKK activation in mice lacking the IKK α subunit of the IκB kinase. Science 284:316–320
  • Iordanov, M. S., Paranjape, J. M., Zhou, A., Wong, J., Williams, B. R. G., Meurs, E. F., Silverman, R. H., and Magun, B. E.. 2000. Activation of p38 mitogen-activated protein kinase and c-jun NH2-terminal kinase by double-stranded RNA and encephalomyocarditis virus: involvement of RNase L, protein kinase R, and alternative pathways. Mol. Cell. Biol. 20:617–627
  • Katze, M. G., Wambach, M., Wong, M. L., Garfinkel, M., Meurs, E., Chong, K., Williams, B. R. G., Hovanessian, A. G., and Barber, G. N.. 1991. Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated 68,000-Mr protein kinase in a cell-free system. Mol. Cell. Biol. 11:5497–5505
  • Knighton, D. R., Zheng, J. H., Ten Eyck, L. F., Xuong, N. H., Taylor, S. S., and Sowadski, J. M.. 1991. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253:414–420
  • Kopp, E., and Gosh, S.. 1995. NF-κB: ten years after. Adv. Immunol. 58:1–27
  • Kumar, A., Haque, J., Lacoste, J., Hiscott, J., and Williams, B. R. G.. 1994. The dsRNA-dependent protein kinase, PKR, activates transcription factor NF-κB by phosphorylating IκB. Proc. Natl. Acad. Sci. USA 91:6288–6292
  • Kumar, A., Yang, Y. L., Flati, V., Der, S., Kadereit, S., Deb, A., Hapque, J., Reis, L., Weissmann, C., and Williams, B. R.. 1996. Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-κB. EMBO J. 16:406–416
  • Laurent, A. G., Krust, B., Galabru, J., Svab, J., and Hovanessian, A. G.. 1985. Monoclonal antibodies to interferon induced 68,000 Mr protein and their use for the detection of double-stranded RNA dependent protein kinase in human cells. Proc. Natl. Acad. Sci. USA 82:4341–4345
  • Lee, F., Hagler, J., Chen, Z., and Maniatis, T.. 1997. Activation of the IκB α complex by MEKK1, a kinase of the JNK pathway. Cell 88:213–222
  • Li, Q., Van Antwerp, D., Mercurio, F., Lee, K., and Verma, I.. 1999. Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284:321–325
  • Li, X., Commane, M., Burns, C., Vithalani, K., Cao, Z., and Stark, G. R.. 1999. Mutant cells that do not respond to interleukin-1 (IL-1) reveal a novel role for IL-1 receptor-associated kinase. Mol. Cell. Biol. 19:4643–4652
  • Li, X. L., Blackford, J. A., and Hassel, B. A.. 1998. RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J. Virol. 72:2752–2759
  • Malinin, N., Boldin, M., Kovalenko, A., and Wallach, D.. 1997. MAP3K-related kinase involved in NF-κB induction by TNF, CD95 and IL-1. Nature 385:540–544
  • Mamane, Y., Heylbroeck, C., Génin, P., Algarté, M., Servant, M. J., LePage, C., DeLuca, C., Kwon, H., Lin, R., and Hiscott, J.. 1999. Interferon regulatory factors: the next generation. Gene 237:1–14
  • Maran, A., Maitra, R. K., Kumar, A., Dong, B., Xiao, W., Li, G., Williams, B. R., Torrence, P. F., and Silverman, R. H.. 1994. Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras. Science 265:789–792
  • Maran, A., Waller, C. F., Paranjape, J. M., Li, G., Xiao, W., Zhang, K. et al. 1998. 2′,5′-Oligoadenylate-antisense chimeras cause RNAse L to selectively degrade bcr/abl mRNA in chronic myelogenous leukemia cells. Blood 92:4336–4343
  • McCarthy, J. V., Ni, J., and Dixit, V. M.. 1998. RIP2 is a novel NF-κB-activating and cell death-inducing kinase. J. Biol. Chem. 273:16968–16975
  • Mercurio, F., Zhu, H., Murray, B., Shevchenko, A., Bennett, B., Li, J., Young, D., Barbosa, M., Mann, M., Manning, A., and Rao, A.. 1997. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278:860–866
  • Meurs, E., Chong, K., Galabru, J., Thomas, S. B., Kerr, I. M., Williams, B. R. G., and Hovanessian, A. G.. 1990. Molecular cloning and characterization of cDNA encoding human double-stranded RNA activated protein kinase induced by interferon. Cell 62:379–390
  • Meurs, E. F., McMillan, N., Williams, B. R., Hovanessian, A. G., and Southern, P. J.. 1995. Human PKR transfected into murine cells stimulates expression of genes under control of the HIV1 or HTLV-1 LTR. Virology 214:653–659
  • Meurs, E. F., Watanabe, Y., Kadereit, S., Barber, G. N., Katze, M. G., Chong, K., Williams, B. R. G., and Hovanessian, A. G.. 1992. Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eucaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth. J. Virol. 66:5805–5814
  • Munoz, E., Courtois, G., Veschambre, P., Jalinot, P., and Israel, A.. 1994. Tax induces nuclear translocation of NF-κB through dissociation of cytoplasmic complexes containing p105 or p100 but does not induce degradation of IκBα/MAD3. J. Virol. 68:8035–8044
  • Nagai, K., Hoi-Tao Wong, A., Li, S., Wai Ning Tam, N., Cuddihy, A. R., Sonenberg, N., Mathews, M. B., Hiscott, J., Wainberg, M. A., and Koromilas, A. E.. 1997. Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR. J. Virol. 71:1718–1725
  • Patel, R. C., Stanton, P., and Sen, G. C.. 1996. Specific mutations near the amino terminus of double-stranded RNA-dependent protein kinase (PKR) differentially affect its double-stranded RNA binding and dimerization properties. J. Biol. Chem. 271:25657–25663
  • Regnier, C. H., Song, H. Y., Gao, X., Goeddel, D. V., Cao, Z., and Rothe, M.. 1997. Identification and characterization of an IkappaB kinase. Cell 90:373–383
  • Rothwarf, D., Zandi, E., Natoli, G., and Karin, M.. 1998. IKK-γ is an essential regulatory subunit of the IκB kinase complex. Nature 395:297–300
  • Samuel, C. E.. 1991. Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. Virology 183:1–11
  • Santoyo, J., Alcalde, J., Mendez, R., Pulido, D., and De Haro, C.. 1997. Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2α (eIF-2α) kinase from Drosophila melanogaster. J. Biol. Chem. 272:12544–12550
  • Seeler, J. S., Marchio, A., Sitterlin, D., Transy, C., and Dejean, A.. 1998. Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc. Natl. Acad. Sci. USA 95:7316–7321
  • Shi, Y., Vattem, K. M., Sood, R., An, J., Liang, J., Stramm, L., and Wek, R. C.. 1998. Identification and characterization of pancreatic eukaryotic initiation factor 2 α-subunit, PEK, involved in translational control. Mol. Cell. Biol. 18:7499–7509
  • Stancovski, I., and Baltimore, D.. 1997. NF-κB activation: the IκB kinase revealed? Cell 91:299–302
  • Takeda, K., Takeuchi, O., Tsujimura, T., Itami, S., Adachi, O., Kawai, T., Sanjo, H., Yoshikawa, K., Terada, N., and Akira, S.. 1999. Limb and skin abnormalities in mice lacking IKKα. Science 284:313–316
  • Ting, A. T., Pimentel-Muinos, F. X., and Seed, B.. 1996. RIP mediates tumor necrosis factor receptor 1 activation of NF-κB but not Fas/APO-1-initiated apoptosis. EMBO J. 15:6189–6196
  • Watanabe, M., Muramatsu, M., Hirai, H., Suzuki, T., Fujisawa, J., Yoshida, M., Arai, K., and Arai, N.. 1993. HTLV-1 encoded Tax in association with NF-κB precursor p105 enhances nuclear localization of NF-κB p50 and p65 in transfected cells. Oncogene 8:2949–2958
  • Williams, B. R. G.. 1995. The role of the dsRNA-activated protein kinase, PKR, in signal transduction. Semin. Virol. 6:191–202
  • Yamaoka, S., Courtois, G., Bessia, C., Whiteside, S. T., Weil, R., Agout, F., Kirk, H. E., Kay, R. J., and Israel, A.. 1998. Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation. Cell 93:1231–1240
  • Yang, Y. L., Reis, L. F., Pavlovic, J., Aguzzi, A., Schafer, R., Kumar, A., Williams, B. R., Aguet, M., and Weissmann, C.. 1995. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14:6095–6106
  • Yaron, A., Gonen, H., Alkalay, I., Hatzubai, A., Jung, S., Beyth, S., Mercurio, F., Manning, A., Ciechanover, A., and Ben-Neriah, Y.. 1997. Inhibition of NF-κB cellular function via specific targeting of the IκB ubiquitin ligase. EMBO J. 16:101–107
  • Yu, P. W., Huang, B. C. B., Shen, M., Quast, J., Chan, E., Xu, X., Nolan, G. P., Payan, D. G., and Luo, Y.. 1999. Identification of RIP3, a RIP-like kinase that activates apoptosis and NF-κB. Curr. Biol. 9:539–542
  • Zandi, E., Rothwarf, D. M., Delhasse, M., Hayakawa, M., and Karin, M.. 1997. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91:243–252
  • Zhou, A., Hassel, B. A., and Silverman, R. H.. 1993. Expression cloning of 2-5A-dependent RNAse: a uniquely regulatory mediator of interferon action. Cell 72:753–765
  • Zinn, K., Keller, A., Whittemore, L. A., and Maniatis, T.. 1988. 2-Aminopurine selectively inhibits the induction of β-interferon, c-fos, and c-myc gene expression. Science 240:210–213

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