Activation of the heterodimeric IκB kinase α (IKKα)-IKKβ complex is directional: IKKα regulates IKKβ under both basal and stimulated conditions

Molecular and Cellular Biology

Volumn 20, Issue 4, 2000, Pages 1170-1178

  O'Mahony, Alison ^b   Lin, Xin ^b   Geleziunas, Romas ^b   Greene, Warner C ^a,b  

^a GLADSTONE INSTITUTE OF VIROLOGY AND IMMUNOLOGY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PROTEIN KINASE C; CHUK PROTEIN, HUMAN; I KAPPA B KINASE; IKBKB PROTEIN, HUMAN; IKBKE PROTEIN, HUMAN; MAP3K1 PROTEIN, HUMAN; MAP3K8 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 1; ONCOPROTEIN; PROTEIN SERINE THREONINE KINASE; RECOMBINANT PROTEIN; TAX PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; CELL LINE; CHEMISTRY; DIMERIZATION; GENETICS; HELA CELL; METABOLISM; MUTATION; PHOSPHORYLATION; PROTEIN QUATERNARY STRUCTURE;

CELL LINE; DIMERIZATION; ENZYME ACTIVATION; GENE PRODUCTS, TAX; HELA CELLS; HUMANS; I-KAPPA B KINASE; MAP KINASE KINASE KINASE 1; MAP KINASE KINASE KINASES; MUTATION; PHOSPHORYLATION; PROTEIN STRUCTURE, QUATERNARY; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0033621618     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.20.4.1170-1178.2000     Document Type: Article

References (64)

1. Baeuerle, P. A., and D. Baltimore. 1996. NF-κB: ten years after. Cell 87: 13-20.
2. Baldwin, A. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14:649-683.
3. Beg, A. A., and A. J. Baldwin. 1993. The IκB proteins: multifunctional regulators of Rel/NF-κB transcription factors. Genes Dev. 7:2064-2070.
4. Beg, A. A., W. C. Sha, R. T. Bronson, S. Ghosh, and D. Baltimore. 1995. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376:167-170.
5. Belvin, M. P., and K. V. Anderson. 1996. A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu. Rev. Cell Dev. Biol. 12:393-416.
6. Beraud, C., S. C. Sun, P. Ganchi, D. W. Ballard, and W. C. Greene. 1994. Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-κB2 p100 gene product: implications for viral latency. Mol. Cell. Biol. 14:1374-1382.
7. Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist. 1995. Control of IκB-alpha proteolysis by site-specific, signal-induced phosphorylation. Science 267:1485-1488.
8. Chen, Z., J. Hagler, V. J. Palombella, F. Melandri, D. Scherer, D. Ballard. and T. Maniatis. 1995. Signal-induced site-specific phosphorylation targets IκB alpha to the ubiquitin-proteasome pathway. Genes Dev. 9:1586-1597.
9. Chu, Z.-L., Y.-A. Shin, J.-M. Yang, J. A. DiDonato, and D. A. Ballard. 1999. IKKγ mediates the interaction of cellular IκB kinases with the Tax transforming protein of human T cell leukemia virus type I. J. Biol. Chem. 274: 15297-15300.
10. Chu, Z. L., J. A. DiDonato, J. Hawiger, and D. W. Ballard. 1998. The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IκB kinases containing IKKα and IKKβ. J. Biol. Chem. 273:15891-15894.
11. Cohen, L., W. J. Henzel, and P. A. Baeuerle. 1998. IKAP is a scaffold protein of the IαB kinase complex. Nature 395:292-296.
12. Delhase, M., M. Hayakawa, Y. Chen, and M. Karin. 1999. Positive and negative regulation of the IκB kinase activity through IKKβ subunit phosphorylation. Science 284:309-313.
13. DiDonato, J., F. Mercurio, C. Rosette, L. J. Wu, H. Suyang, S. Ghosh, and M. Karin. 1996. Mapping of the inducible IκB phosphorylation sites that signal its ubiquitination and degradation. Mol. Cell. Biol. 16:1295-304.
14. 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.
15. Fischer, C., S. Page, M. Weber, T. Eisele, D. Neumeier, and K. Brand. 1999. Differential effects of lipopolysaccharide and tumor necrosis factor on monocytic IκB kinase signalsome activation and IκB proteolysis. J. Biol. Chem. 274:24625-24632.
16. Geleziunas, R., S. Ferrell, X. Lin, Y. Mu, E. J. Cunningham, M. Grant, M. A. Connelly, J. E. Hambor, K. B. Marcu, and W. C. Greene. 1998. Human T-cell leukemia virus type 1 Tax induction of NF-κB involves activation of the IκB kinase alpha (IKKα) and IKKβ cellular kinases. Mol. Cell. Biol. 18:5157-5165.
17. Ghosh, S., M. J. May, and E. B. Kopp. 1998. NF-κB and Rel proteins: evolutionary conserved mediators of immune responses. Annu. Rev. Immunol. 16:225-260.
18. Harhaj, E. W., and S.-C. Sun. 1999. IKKγ serves as a docking subunit of the IκB kinases (IKK) and mediates interaction of IKK with the human T-cell leukemia virus Tax protein. J. Biol. Chem. 274:22911-22914.
19. Hirano, M., S. Osada, T. Aoki, S. Hirai, M. Hosaka, J. Inoue, and S. Ohno. 1996. MEK kinase is involved in tumor necrosis factor alpha-induced NF-κB activation and degradation of IκB-α. J. Biol. Chem. 271:13234-13238.
20. Hsu, H., H. B. Shu, M. G. Pan, and D. V. Goeddel. 1996. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299-308.
21. 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 the IκB kinase. Science 284: 316-320.
22. Jin, D.-Y., V. Giordano, K. V. Kibler, H. Nakano, and K.-T. Jeang. 1999. Role of adapter function in oncoprotein-mediated activation of NF-κB. J. Biol. Chem. 274:17402-17405.
23. Kelliher, M. A., S. Grimm, Y. Ishida, F. Kuo, B. Z. Stanger, and P. Leder. 1998. The death domain kinase RIP mediates the TNF-induced NF-κB signal. Immunity 8:297-303.
24. Kempiak, S. J., T. S. Hiura, and A. E. Nel. 1999. The Jun kinase cascade is responsible for activating the CD28 response element of the IL-2 promoter: proof of cross-talk with the IκB kinase cascade. J. Immunol. 162:3176-3187.
25. Kirschning, C. J., H. Wesche, T. Merrill Ayres, and M. Rothe. 1998. Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J. Exp. Med. 188:2091-2097.
26. Klement, J. F., N. R. Rice, B. D. Car, S. J. Abbondanzo, G. D. Powers, H. Bhatt, C.-H. Chen, C. A. Rosen, and C. L. Stewart. 1996. IκB alpha deficiency results in a sustained NF-κB response and severe widespread dermatitis in mice. Mol. Cell. Biol. 16:2341-2349.
27. Lee, F. S., J. Hagler, Z. J. Chen, and T. Maniatis. 1997. Activation of the IκB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell 88: 213-222.
28. Lee, F. S., R. T. Peters, L. C. Dang, and T. Maniatis. 1998. MEKK1 activates both IκB kinase a and IκB kinase β. Proc. Natl. Acad. Sci. USA 95:9319-9324.
29. Li, J., G. W. Peet, Pullen S. S., J. Schembri-King, T. C. Warren, K. B. Marcu, M. R. Kehry, R. Barton, and S. Jakes. 1998. Recombinant IκB kinases α and β are direct kinases of IκBα. J. Biol. Chem. 273:30736-30741.
30. Li, Q., Q. Lu, J. Y. Hwang, D. Buscher, K.-F. Lee, J. C. Izpisua-Belmonte, and I. M. Verma. 1999. The IKK1-deficient mice exhibit abnormal development of skin and skeleton. Genes Dev. 13:1322-1328.
31. 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.
32. Li, Z.-W., W. Chu, Y. Hu, M. Delhase, T. Deerinck, M. Ellisman, R. Johnson, and M. Karin. 1999. The IKKβ subunit of IκB kinase (IKK) is essential for nuclear factor-κB activation and prevention of apoptosis. J. Exp. Med. 189: 1839-1845.
33. Lin, X., E. T. Cunningham, 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.
34. Lin, X., Y. Mu, E. T. Cunningham, K. B. Marcu, R. Geleziunas, and W. C. Greene. 1998. Molecular determinants of NF-κB-inducing kinase action. Mol. Cell. Biol. 18:5899-5907.
35. 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.
36. 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-I. Nature 385:540-544.
37. May, M. J., and S. Ghosh. IW. Rel/NF-κB and IκB proteins: an overview. Semin. Cancer Biol. 8:63-73.
38. 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)-associated protein 1, a common component of the heterogeneous IKK complex. Mol. Cell. Biol. 19:1526-1538.
39. Mercurio, F., H. Zhu, B. W. Murray, A. Shevehenko, B. L. Bennett, J. Li, D. B. Young, M. Barbosa, M. Mann, A. Manning, and A. Kao. 1997. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278:860-866.
40. Meyer, C. F., X. Wang, C. Chang, D. Templeton, and T. H. Tan. 1996. Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating κB enhancer activation. J. Biol. Chem. 271:8971-8976.
41. Nakano, H., M. Shindo, S. Sakon, S. Nishinaka, M. Mihara, H. Yagita, and K. Okumura. 1998. Differential regulation of IκB kinase alpha and beta by two upstream kinases. NF-κB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc. Natl. Acad. Sci. USA 95:3537-3542.
42. 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.
43. O'Connell, M. A., B. L. Bennett, F. Mercurio, A. M. Manning, and N. Mackman. 1998. Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells. J. Biol. Chem. 273:30410-30414.
44. Regnier, C. H., H. Y. Song, X. Gao, D. V. Goeddel, Z. Cao, and M. Rothe. 1997. Identification and characterization of an IκB kinase. Cell 90:373-383.
45. Rothe, M., V. Sarma, V. M. Dixit, and D. V. Goeddel. 1995. TRAF2-mediated activation of NF-κB by TNF receptor 2 and CD40. Science 269:1424-1427.
46. 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.
47. Scherer, D. C., J. A. Brockman, Z. Chen, T. Maniatis, and D. W. Ballard. 1995. Signal-induced degradation of I κBα requires site-specific ubiquitination. Proc. Natl. Acad. Sci. USA 92:11259-11263.
48. Smith, M. R., and W. C. Greene. 1990. Identification of HTLV-I tax transactivator mutants exhibiting novel transcriptional phenotypes. Genes Dev. 4: 1875-85.
49. 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.
50. Sun, S., J. Elwood, and W. C. Greene. 1996. Both amino-and carboxylterminal sequences within IκBα regulate its inducible degradation. Mol. Cell. Biol. 16:1058-1065.
51. 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.
52. Tanaka, M., M. E. Fuentes, K. Yamaguchi, M. H. Durnin, S. A. Dalrymple, K. L. Hardy, and D. V. Goeddel. 1999. Embryonic lethality, liver degeneration and impaired NF-κB activation in IKK-beta-deficient mice. Immunity 10:421-429.
53. Thanos, D., and T. Maniatis. 1995. NF-κB: a lesson in family values. Cell 80: 529-532.
54. Ting, A. T., M. F. Pimentel, and B. Seed. 1996. RIP mediates tumor necrosis factor receptor 1 activation of NF-κB but not Fas/APO-1-initiated apoptosis. EMBO J. 15:6189-6196.
55. 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.
56. Uhlik, M., L. Good, G. Xiao, E. W. Harhaj, E. Zandi, M. Karin, and S. C. Sun. 1998. NF-κB-inducing kinase and IκB kinase participate in human T-cell leukemia virus I Tax-mediated NF-κB activation. J. Biol. Chem. 273: 21132-21136.
57. Verma, I. M., J. K. Stevenson, E. M. Schwarz, A. D. Van, and S. Miyamoto. 1995. Rel/NF-κB/IκB family: intimate tales of association and dissociation. Genes Dev. 9:2723-2735.
58. Woronicz, J. D., X. Gao, Z. Cao, M. Rothe, and D. V. Goeddel. 1997. IκB kinase-β: NF-κB activation and complex formation with IκB kinase-α and NIK. Science 278:866-869.
59. 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.
60. Yang, R. B., M. R. Mark, A. Gray, A. Huang, M. H. Xie, M. Zhang, A. Goddard, W. I. Wood, A. L. Gurney, and P. J. Godowski. 1998. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395:284-288.
61. 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-1 Tax protein binds to MEKK1 to stimulate IκB kinase activity and NF-κB activation. Cell 93: 875-884.
62. Zandi, E., Y. Chen, and M. Karin. 1998. Direct phosphorylation of IκB by IKKα and IKKβ: discrimination between free and NF-κB-bound substrate. Science 281:1360-1363.
63. Zandi, E., and M. Karin. 1999. Bridging the gap: composition, regulation and physiological function of the IκB kinase complex. Mol. Cell. Biol. 19: 4547-4551.
64. 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.