NF-κB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-κB-inducing kinase and IκB kinase

Molecular and Cellular Biology

Volumn 20, Issue 4, 2000, Pages 1278-1290

  Zamanian Daryoush, Maryam ^b   Mogensen, Trine H ^a,b   DiDonato, Joseph A ^b   Williams, Bryan R G ^b  

^a AARHUS UNIVERSITY   (Denmark)

^b LERNER RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOUBLE STRANDED RNA; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PHOSPHOTRANSFERASE; PROTEIN SERINE THREONINE KINASE; TUMOR NECROSIS FACTOR ALPHA; CHUK PROTEIN, HUMAN; CHUK PROTEIN, MOUSE; I KAPPA B KINASE; IKBKB PROTEIN, HUMAN; IKBKB PROTEIN, MOUSE; IKBKE PROTEIN, HUMAN; IKBKE PROTEIN, MOUSE; NF KAPPA B KINASE; NF-KAPPA B KINASE; POLYINOSINIC POLYCYTIDYLIC ACID; PROTEIN KINASE R;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVATION; ENZYME ANALYSIS; ENZYME INDUCTION; ENZYME KINETICS; ENZYME MECHANISM; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RNA TRANSCRIPTION; ANIMAL; CELL LINE; DRUG EFFECT; GENETIC TRANSFECTION; GENETICS; KINETICS; METABOLISM; MOUSE MUTANT; SIGNAL TRANSDUCTION;

ANIMALS; CELL LINE; EIF-2 KINASE; ENZYME ACTIVATION; HUMANS; I-KAPPA B KINASE; KINETICS; MICE; MICE, KNOCKOUT; NF-KAPPA B; POLY I-C; PROTEIN-SERINE-THREONINE KINASES; RNA, DOUBLE-STRANDED; SIGNAL TRANSDUCTION; TRANSFECTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0033621619     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.20.4.1278-1290.2000     Document Type: Article

References (104)

1. Balachandran, S., C. N. Kim, W. C. Yeh, T. W. Mak, K. Bhalla, and G. N. Barber. 1998. Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling. EMBO J. 17: 6888-6902.
2. Baldwin, A. S., Jr. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14:649-683.
3. Barber, G. N., M. Wambach, S. Thompson, R. Jagus, and M. G. Katze. 1995. Mutants of the RNA-dependent protein kinase (PKR) lacking double-stranded RNA binding domain I can act as transdominant inhibitors and induce malignant transformation. Mol. Cell. Biol. 15:3138-3146.
4. Beg, A. A., T. S. Finco, P. V. Nantermet, and A. S. Baldwin, Jr. 1993. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IκBα: a mechanism for NF-κB activation. Mol. Cell. Biol. 13:3301-3310.
5. Beraud, C., W. J. Henzel, and P. A. Baeuerle. 1999. Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-κB activation. Proc. Natl. Acad. Sci. USA 96:429-434.
6. Brockman, J. A., D. C. Scherer, T. A. McKinsey, S. M. Hall, X. Qi, W. Y. Lee, and D. W. Ballard. 1995. Coupling of a signal response domain in IκBκ to multiple pathways for NF-κB activation. Mol. Cell. Biol. 15:2809-2818.
7. Carpick, B. W., V. Graziano, D. Schneider, R. K. Maitra, X. Lee, and B. R. G. Williams. 1997. Characterization of the solution complex between the interferon-induced, double-stranded RNA-activated protein kinase and HIV-I transactivating region RNA. J. Biol. Chem. 272:9510-9516.
8. Chen, Z., J. Hagler, V. J. Palombella, F. Melandri, D. Scherer, D. Ballard, and T. Maniatis. 1995. Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev. 9:1586-1597.
9. Cheshire, J. L., B. R. Williams, and A. S. Baldwin, Jr. 1999. Involvement of double-stranded RNA-activated protein kinase in the synergistic activation of nuclear factor-κB by tumor necrosis factor-alpha and gamma-interferon in preneuronal cells. J. Biol. Chem. 274:4801-4806.
10. Chiao, P. J., S. Miyamoto, and I. M. Verma. 1994. Autoregulation of IκBα activity. Proc. Natl. Acad. Sci. USA 91:28-32.
11. Chong, K. L., L. Feng, K. Schappert, E. Meurs, T. F. Donahue, J. D. Friesen, A. G. Hovanessian, and B. R. Williams. 1992. Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J. 11:1553-1562.
12. Clemens, M. J., and A. Elia. 1997. The double-stranded RNA-dependent protein kinase PKR: structure and function. J. Interferon Cytokine Res. 17:503-524.
13. Cohen, L., W. J. Henzel, and P. A. Baeuerle. 1998. IKAP is a scaffold protein of the IκB kinase complex. Nature 395:292-296.
14. Cuddihy, A. R., S. Li, N. W. Tam, A. H. Wong, Y. Taya, N. Abraham, J. C. Bell, and A. E. Koromilas. 1999. Double-stranded-RNA-activated protein kinase PKR enhances transcriptional activation by tumor suppressor p53. Mol. Cell. Biol. 19:2475-2484.
15. Cuddihy, A. R., A. H. Wong, N. W. Tam, S. Li, and A. E. Koromilas. 1999. The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. Oncogene 18:2690-2702.
16. de Haro, C., R. Mendez, and J. Santoyo. 1996. The eIF-2α kinases and the control of protein synthesis. FASEB J. 10:1378-1387.
17. Delhase, M., M. Hayakawa, Y. Chen, and M. Karin. 1999. Positive and negative regulation of IκB kinase activity through IΚΚβ subunit phosphorylation. Science 284:309-313.
18. de Martin, R., B. Vanhove, Q. Cheng, E. Hofer, V. Csizmadia, H. Winkler, and F. H. Bach. 1993. Cytokine-inducible expression in endothelial cells of an iκBα-like gene is regulated by NF-κB. EMBO J. 12:2773-2779.
19. Der, S. D., and A. S. Lau. 1995. Involvement of the double-stranded-RNA-dependent kinase PKR in Interferon expression and interferon-mediated antiviral activity. Proc. Natl. Acad. Sci. USA 92:8841-8845.
20. Der, S. D., Y. L. Yang, C. Weissmann, and B. R. Williams. 1997. A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis. Proc. Natl. Acad. Sci. USA 94:3279-3283.
21. DiDonato, J. A., M. Hayakawa, D. M. Rothwarf, E. Zandi, and M. Karin. 1997. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388:548-554.
22. Donze, O., J. Dostie, and N. Sonenberg. 1999. Regulatable expression of the interferon-induced double-stranded RNA dependent protein kinase PKR induces apoptosis and fas receptor expression. Virology 256:322-329.
23. Elewaut, D., J. A. DiDonato, J. M. Kim, F. Truong, L. Eckmann, and M. F. Kagnoff. 1999. NF-κB is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. J. Immunol. 163:1457-1466.
24. Finco, T. S., and A. S. Baldwin. 1995. Mechanistic aspects of NF-κB regulation: the emerging role of phosphorylation and proteolysis. Immunity 3:263-272.
25. Galabru, J., and A. G. Hovanessian. 1985. Two interferon-induced proteins are involved in the protein kinase complex dependent on double-stranded RNA. Cell 43:685-694.
26. Ghosh, S., M. J. May, and E. B. Kopp. 1998. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225-260.
27. Gusella, G. L., T. Musso, S. E. Rottschafer, K. Pulkki, and L. Varesio. 1995. Potential requirement of a functional double-stranded RNA-dependent protein kinase (PKR) for the tumoricidal activation of macrophages by lipopolysaccharide or IFN-α/β but not IFN-γ. J. Immunol. 154:345-354.
28. He, J., J. J. Olson, A. J. Ekstrand, A. Serbanescu, J. Yang, M. K. Offermann, and C. D. James. 1996. Transfection of IFN-α in human glioblastoma cells and tumorigenicity in association with induction of PKR and OAS gene expression. J. Neurosurg. 85:1085-1090.
29. Hovanessian, A. G. 1989. The double stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. J. Interferon Res. 9:641-647.
30. Hu, Y., V. Baud, M. Delhase, P. Zhang, T. Deerinck, M. Ellisman, R. Johnson, and M. Karin. 1999. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of IκB kinase. Science 284: 316-320.
31. Imbert, V., R. A. Rupec, A. Livolsi, H. L. Pahl, E. B. Traenckner, C. Mueller-Dieckmann, D. Farahifar, B. Rossi, P. Auberger, P. A. Baeuerle, and J. F. Peyron. 1996. Tyrosine phosphorylation of IκB-α activates NF-κB without proteolytic degradation of IκB-α. Cell 86:787-798.
32. Ito, C. Y., A. G. Kazantsev, and A. S. Baldwin, Jr. 1994. Three NF-κB sites in the IκB-α promoter are required for induction of gene expression by TNF α. Nucleic Acids Res. 22:3787-3792.
33. Katze, M. G. 1995. Regulation of the interferon-induced PKR: can viruses cope? Trends Microbiol. 3:75-78.
34. Kerr, I. M., R. E. Brown, and A. G. Hovanessian. 1977. Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA. Nature 268:540-542.
35. Kibler, K. V., T. Shors, K. B. Perkins, C. C. Zeman, M. P. Banaszak, J. Biesterfeldt, J. O. Langland, and B. L. Jacobs. 1997. Double-stranded RNA is a trigger for apoptosis in vaccinia virus-infected cells. J. Virol. 71:1992-2003.
36. Kirchhoff, S., A. E. Koromilas, F. Schaper, M. Grashoff, N. Sonenberg, and H. Hauser. 1995. IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR. Oncogene 11:439-445.
37. Koromilas, A. E., S. Roy, G. N. Barber, M. G. Katze, and N. Sonenberg. 1992. Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. Science 257:1685-1689.
38. Krust, B., J. Galabru, and A. G. Hovanessian. 1984. Further characterization of the protein kinase activity mediated by interferon in mouse and human cells. J. Biol. Chem. 259:8494-8498.
39. Kumar, A., J. Haque, J. Lacoste, J. Hiscott, and B. R. G. Williams. 1994. Double-stranded RNA-dependent protein kinase activates transcription factor NF-κB by phosphorylating IκB. Proc. Natl. Acad. Sci. USA 91:6288-6292.
40. Kumar, A., Y. L. Yang, V. Flati, S. Der, S. Kadereit, A. Deb, J. Haque, L. Reis, C. Weissmann, and B. R. Williams. 1997. 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.
41. Leaman, D. W., A. Salvekar, R. Patel, G. C. Sen, and G. R. Stark. 1998. A mutant cell line defective in response to double-stranded RNA and in regulating basal expression of interferon-stimulated genes. Proc. Natl. Acad. Sci. USA 95:9442-9447.
42. Lee, F. S., J. Hagler, Z. J. Chen, and T. Maniatis. 1997. Activation of the IκB α kinase complex by MEKK1, a kinase of the JNK pathway. Cell 88:213-222.
43. Lee, S. B., and M. Esteban. 1994. The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology 199:491-496.
44. Lee, S. B., Z. Melkova, W. Yan, B. R. Williams, A. G. Hovanessian, and M. Esteban. 1993. The interferon-induced double-stranded RNA-activated human p68 protein kinase potently inhibits protein synthesis in cultured cells. Virology 192:380-385.
45. Lee, S. B., D. Rodriguez, J. R. Rodriguez, and M. Esteban. 1997. The apoptosis pathway triggered by the interferon-induced protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases. Virology 231:81-88.
46. Li, N., and M. Karin. 1998. Ionizing radiation and short wavelength UV activate NF-κB through two distinct mechanisms. Proc. Natl. Acad. Sci. USA 95:13012-13017.
47. Li, Q., D. Van Antwerp, F. Mercurio, K. F. Lee, and I. M. Verma. 1999. Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284:321-325.
48. Lin, X., E. T. Cunningham, Jr., Y. Mu, R. Geleziunas, and W. C. Greene. 1999. The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-κB acting through the NF-κB-inducing kinase and IκB kinases. Immunity 10:271-280.
49. Ling, L., Z. Cao, and D. V. Goeddel. 1998. NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176. Proc. Natl. Acad. Sci. USA 95:3792-3797.
50. Malinin, N. L., M. P. Boldin, A. V. Kovalenko, and D. Wallach. 1997. MAP3K-related kinase involved in NF-κB induction by TNF. CD95 and IL-1. Nature 385:540-544.
51. Mercurio, F., B. W. Murray, A. Shevchenko, B. L. Bennett, D. B. Young, J. W. Li, G. Pascual, A. Motiwala, H. Zhu, M. Mann, and A. M. Manning. 1999. IκB kinase (IKK)-associaled protein 1, a common component of the heterogeneous IKK complex. Mol. Cell. Biol. 19:1526-1538.
52. Mercurio, F., H. Zhu, B. W. Murray, A. Shevchenko, B. L. Bennett, J. Li, D. B. Young, M. Barbosa, M. Mann, A. Manning, and A. Rao. 1997. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278:860-866.
53. Meurs, E., K. Chong, J. Galabru, N. S. Thomas, I. M. Kerr, B. R. Williams, and A. G. Hovanessian. 1990. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell 62:379-390.
54. Meurs, E. F., J. Galabru, G. N. Barber, M. G. Katze, and A. G. Hovanessian. 1993. Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. Proc. Natl. Acad. Sci. USA 90:232-236.
55. Meurs, E. F., Y. Watanabe, S. Kadereit, G. N. Barber, M. G. Katze, K. Chong, B. R. Williams, and A. G. Hovanessian. 1992. Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth. J. Virol. 66:5804-5814.
56. Miyamoto, S., and I. M. Verma. 1995. Rel/NF-κB/IκB story. Adv. Cancer Res. 66:255-292.
57. Mundschau, L. J., and D. V. Faller. 1992. Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. J. Biol. Chem. 267:23092-23098.
58. Mundschau, L. J., and D. V. Faller. 1995. Platelet-derived growth factor signal transduction through the interferon-inducible kinase PKR. Immediate early gene induction. J. Biol. Chem. 270:3100-3106.
59. Naumann, M., and C. Scheidereit. 1994. Activation of NF-κB in vivo is regulated by multiple phosphorylations. EMBO J. 13:4597-4607.
60. Nemoto, S., J. A. DiDonato, and A. Lin. 1998. Coordinate regulation of IκB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-κB-inducing kinase. Mol. Cell. Biol. 18:7336-7343.
61. Ninomiya-Tsuji, J., K. Kishimoto, A. Hiyama, J. Inoue, Z. Cao, and K. Matsumoto. 1999. The kinase TAK1 can activate the NIK-I κB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398:252-256.
62. O'Connell, M. A., B. L. Bennett, F. Mercurio, A. M. Manning, and N. Mackman. 1998. Role of IKK2 and IKK2 in lipopolysaccharide signaling in human monocytic cells. J. Biol. Chem. 273:30410-30414.
63. Ohmori, Y., J. Tebo, S. Nedospasov, and T. A. Hamilton. 1994 κB binding activity in a murine macrophage-like cell line. Sequence-specific differences in κB binding and transcriptional activation functions. J. Biol. Chem. 269: 17684-17690.
64. Pain, V. M. 1996. Initiation of protein synthesis in eukaryotic cells. Eur. J. Biochem. 236:747-771.
65. Petryshyn, R., J. J. Chen, L. Danley, and R. L. Matts. 1996. Effect of interferon on protein translation during growth stages of 3T3 cells. Arch. Biochem. Biophys. 326:290-297.
66. Petryshyn, R., J. J. Chen, and I. M. London. 1988. Detection of activated double-stranded RNA-dependent protein kinase in 3T3-F442A cells. Proc. Natl. Acad. Sci. USA 85:1427-1431.
67. Petryshyn, R., J. J. Chen, and I. M. London. 1984. Growth-related expression of a double-stranded RNA-dependent protein kinase in 3T3 cells. J. Biol. Chem. 259:14736-14742.
68. Raveh, T., A. G. Hovanessian, E. F. Meurs, N. Sonenberg, and A. Kimchi. 1996. Double-stranded RNA-dependent protein kinase mediates c-Myc suppression induced by type I interferons. J. Biol. Chem. 271:25479-25484.
69. Regnier, C. H., H. Y. Sung, X. Gao, D. V. Goeddel, Z. Cao, and M. Rothe. 1997. Identification and characterization of an IκB kinase. Cell 90:373-383.
70. Rice, A. P., R. Duncan, J. W. Hershey, and I. M. Kerr. 1985. Double-stranded RNA-dependent protein kinase and 2-5A system are both activated in interferon-treated, encephalomyocarditis virus-infected HeLa cells. J. Virol. 54:894-898.
71. Romano, P. R., S. R. Green, G. N. Barber, M. B. Mathews, and A. G. Hinnebusch. 1995. Structural requirements for double-stranded RNA binding, dimerization. and activation of the human eIF-2α kinase DAI in Saccharomyces cerevisiae. Mol. Cell. Biol. 15:365-378.
72. Rothwarf, D. M., E. Zandi, G. Natoli, and M. Karin. 1998. IKK-γ is an essential regulatory subunit of the IκB kinase complex. Nature 395:297-300.
73. Sakurai, H., H. Miyoshi, W. Toriumi, and T. Sugita. 1999. Functional interactions of transforming growth factor beta-activated kinase 1 with IκB kinases to stimulate NF-κB activation. J. Biol. Chem. 274:10641-10648.
74. Salzberg, S., M. Mandelboim, M. Zalcberg, A. Shainberg, and M. Mandelbaum. 1995. Interruption of myogenesis by transforming growth factor beta 1 or EGTA inhibits expression and activity of the myogenic-associated (2′-5′) oligoadenylate synthetase and PKR. Exp. Cell Res. 219:223-232.
75. Samuel, C. E., R. Duncan, G. S. Knutson, and J. W. Hershey. 1984. Mechanism of interferon action. Increased phosphorylation of protein synthesis initiation factor eIF-2α in interferon-treated, reovirus-infected mouse L929 fibroblasts in vitro and in vivo. J. Biol. Chem, 259:13451-13457.
76. Schmitz, M. L., M. A. dos Santos Silva, and P. A. Baeuerle. 1995. Trans-activation domain 2 (TA2) of p65 NF-κB. Similarity to TAI and phorbol ester-stimulated activity and phosphorylation in intact cells. J. Biol. Chem. 270:15576-15584.
77. Shang, Y., C. R. Baumrucker, and M. H. Green. 1998. c-myc is a major mediator of the synergistic growth inhibitory effects of retinoic acid and interferon in breast cancer cells. J. Biol. Chem. 273:30608-30613.
78. Sizemore, N., S. Leung, and G. R. Stark. 1999. Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-κB p65/RelA subunit. Mol. Cell. Biol. 19:4798-4805.
79. Song, H. Y., C. H. Regnier, C. J. Kirschning, D. V. Goeddel, and M. Rothe. 1997. Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-κB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2. Proc. Natl. Acad. Sci. USA 94:9792-9796.
80. Stark, G. R., I. M. Kerr, B. R. Williams, R. H. Silverman, and R. D. Schreiber. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67:227-264.
81. Sun, S., J. Elwood, and W. C. Greene. 1996. Both amino-and carboxyl-terminal sequences within IκBα regulate its inducible degradation. Mol. Cell. Biol. 16:1058-1065.
82. Sun, S. C., P. A. Ganchi, D. W. Ballard, and W. C. Greene. 1993. NF-κB controls expression of inhibitor IκBα: evidence for an inducible autoregulatory pathway. Science 259:1912-1915.
83. Sylla, B. S., S. C. Hung, D. M. Davidson, E. Hatzivassiliou, N. L. Malinin, D. Wallach, T. D. Gilmore, E. Kieff, and G. Mosialos. 1998 Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-κB through a pathway that includes the NF-κB-inducing kinase and the IκB kinases IKKα and IKKβ. Proc. Natl. Acad. Sci. USA 95:10106-10111.
84. Takeda, K., O. Takeuchi, T. Tsujimura, S. Itami, O. Adachi, T. Kawai, H. Sanjo, K. Yoshikawa, N. Terada, and S. Akira. 1999. Limb and skin abnormalities in mice lacking IKKα. Science 284:313-316.
85. Takizawa, T., K. Ohashi, and Y. Nakanishi. 1996. Possible involvement of double-stranded RNA-activated protein kinase in cell death by influenza virus infection. J. Virol. 70:8128-8132.
86. Thompson, J. E., R. J. Phillips, H. Erdjument-Bromage, P. Tempst, and S. Ghosh. 1995. IκB-β regulates the persistent response in a biphasic activation of NF-κB. Cell 80:573-582.
87. Traenckner, E. B., H. L. Pahl, T. Henkel, K. N. Schmidt, S. Wilk, and P. A. Baeuerle. 1995. Phosphorylation of human IκB-α on serines 32 and 36 controls IκB-α proteolysis and NF-κB activation in response to diverse stimuli. EMBO J. 14:2876-2883.
88. Uehara, T., T. Miyawaki, K. Ohta, Y. Tamara, T. Yokoi, S. Nakamura, and N. Taniguchi. 1992. Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis. Blood 80: 452-458.
89. Van Antwerp, D. J., S. J. Martin, T. Kafri, D. R. Green, and I. M. Verma. 1996. Suppression of TNF-α-induced apoptosis by NF-κB. Science 274:787-789.
90. Wada, N., M. Matsumura, Y. Ohba, N. Kobayashi, T. Takizawa, and Y. Nakanishi. 1995. Transcription stimulation of the Fas-encoding gene by nuclear factor for interleukin-6 expression upon influenza virus infection. J. Biol. Chem. 270:18007-18012.
91. Wang, C. Y., M. W. Mayo, and A. S. Baldwin, Jr. 1996. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274:784-787.
92. Wang, C. Y., M. W. Mayo, R. G. Korneluk, D. V. Goeddel, and A. S. Baldwin, Jr. 1998, NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c. Science 281:1680-1683.
93. Wang, D., and A. S. Baldwin, Jr. 1998. Activation of nuclear factor-κB-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of RelA/p65 on serine 529. J. Biol. Chem. 273: 29411-29416.
94. Whiteside, S. T., M. K. Ernst, O. LeBail, C. Laurent-Winter, N. Rice, and A. Israel. 1995. N-and C-terminal sequences control degradation of MAD3/IκBα in response to inducers of NF-κB activity. Mol. Cell. Biol. 15:5339-5345.
95. Whiteside, S. T., and A. Israel. 1997. IκB proteins: structure, function and regulation. Semin. Cancer Biol. 8:75-82.
96. Woronicz, J. D., X. Gao, Z. Cao, M. Rothe, and D. V. Goeddel. 1997. IκB kinase-beta: NF-κB activation and complex formation with IκB kinase-alpha and NIK. Science 278:866-869.
97. Yamaoka, S., G. Courtois, C. Bessia, S. T. Whiteside, R. Weil, F. Agou, H. E. Kirk, R. J. Kay, and A. Israel. 1998. Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation. Cell 93:1231-1240.
98. Yang, Y. L., L. F. Reis, J. Pavlovic, A. Aguzzi, R. Schafer, A. Kumar, B. R. Williams, M. Aguet, and C. Weissmann. 1995. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14: 6095-6106.
99. Yeung, M. C., J. Liu, and A. S. Lau. 1996. An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells. Proc. Natl. Acad. Sci. USA 93:12451-12455.
100. Yin, M. J., L. B. Christerson, Y. Yamamoto, Y. T. Kwak, S. Xu, F. Mercurio, M. Barbosa, M. H. Cobb, and R. B. Gaynor. 1998. HTLV-I Tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. Cell 93:875-884.
101. Zamanian-Daryoush, M., S. D. Der, and B. R. Williams. 1999. Cell cycle regulation of the double stranded RNA activated protein kinase. PKR. Oncogene 18:315-326.
102. Zandi, E., D. M. Rothwarf, M. Delhase, M. Hayakawa, and M. Karin. 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.
103. Zhao, Q., and F. S. Let. 1999. Mitogen-activated protein kinase/ERK. kinase kinases 2 and 3 activate nuclear factor-κB through IκB kinase-alpha and IκB kinase-beta. J. Biol. Chem. 274:8355-8358.
104. Zhong, H., R. E. Voll, and S. Ghosh. 1998. Phosphorylalion of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol. Cell 1:661-671.