Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway

Genes and Development

Volumn 9, Issue 13, 1995, Pages 1586-1597

  Chen, Zhijian ^a   Hagler, Jeremiah ^b   Palombella, Vito J ^a   Melandri, Francesco ^a   Scherer, David ^c   Ballard, Dean ^c   Maniatis, Tom ^b  

^a MyoGenics Inc   (United States)

^b HARVARD UNIVERSITY   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

I B ; NF B; Phosphorylation; proteasome; Rel; transcription factor; ubiquitin

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INHIBITOR PROTEIN; PROTEASOME; UBIQUITIN;

ARTICLE; HELA CELL; HUMAN; HUMAN CELL; LEUKEMIA CELL LINE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; SIGNAL TRANSDUCTION;

EID: 0029146930     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.9.13.1586     Document Type: Article

References (77)

1. Alkalay, I., A. Yaron, A. Hatzubai, S. Jung, A. Avraham, O. Gerlitz, I. Pashut-Lavon, and Y. Ben-Neriah. 1995. In vivo stimulation of IκB phosphorylation is not sufficient to activate NF-κB. Mol. Cell. Biol. 15: 1294-1301.
2. Baeuerle, P.A. and D. Baltimore. 1988. IκB: A specific inhibitor of the NF-κB transcription factor. Science 242: 540-546.
3. Baeuerle, P.A. and T. Henkel. 1994. Function and activation of NF-κB in the immune system. Annu. Rev. Immunol. 12: 141-179.
4. Beg, A.A. and A.S. Baldwin Jr. 1993, The IκB proteins: Multifunctional regulators of rel/NF-κB transcription factors. Genes &. Dev. 7: 2064-2070.
5. Beg, A.A., S.M. Ruben, R.I. Scheinman, S. Haskill, C.A. Rosen, and A.S. Baldwin Jr. 1992. IκB interacts with the nuclear localization sequences of the subunits of NF-κB: A mechanism for cytoplasmic retention. Genes & Dev. 6: 1899-1913.
6. 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 IκB-α: A mechanism for NF-κB activation. Mol. Cell Biol. 13: 3301-3310.
7. Blank, V., P. Kourilsky, and A. Israel. 1991. Cytoplasmic retention, DNA binding and processing of the NF-κB p50 precursor are controlled by a small region in its C-terminus. EMBO J. 10: 4159-4167.
8. Brockman, J.A., D.C. Scherer, S.M. Hall, T.A. McKinsey, X. Qi, W.Y. Lee, and D.W. Ballard. 1995. Coupling of a signal-response domain in IκBα to multiple pathways for NF-κB activation. Mol. Cell. Biol. 15: 2809-2818.
9. Brown, K., S. Park, T. Kanno, G. Franzoso, and U. Siebenlist. 1993. Mutual regulation of the transcriptional activator NF-κB and its inhibitor, IκB-α. Proc. Natl. Acad. Sci. 90: 2532-2536.
10. Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist. 1995. Control of IκB-α proteolysis by site-specific, signal-induced phosphorylation. Science 267: 1485-1491.
11. Capobianco, A.J., D. Chang, G. Mosialos, and T.D. Gilmore. 1992. p105, the NF-κB p50 precursor protein, is one of the cellular proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells. J. Virol. 66: 3758-3767.
12. Chen, Z. and C.M. Pickart. 1990. A 25-kilodalton ubiquitin carrier protein (E2) catalyzes multiubiquitin chain synthesis via lysine 48 of ubiquitin. J. Biol. Chetn. 265: 21835-21842.
13. Ciechanover, A. 1994. The ubiquitin-proteasome proteolytic pathway. Cell 79: 13-21.
14. Collins, T., M.A. Read, A.S. Neish, M.Z. Whitley, D. Thanos, and T. Maniatis. Transcriptional regulation of endothelial cell adhesion molecules: NF-κB and cytokine-inducible enhancers. FASEB J. (in press).
15. Cordle, S.R., R. Donald, M.A. Read, and J. Hawiger. 1993. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-κB proteins in human monocytic THP-1 cells. J. Biol. Chem. 268: 11803-11810.
16. Diaz-Meco, M.T., L.S. Dominguez, P. Dent, J. Lozano, M.M. Municio, E. Berra, R.T. Hay, T.W. Sturgill, and J. Moscat. 1994. ζPKC induces phosphorylation and inactivation of IκB-α in vitro. EMBO J. 13: 2842-2848.
17. DiDonato, J.A., F. Mercurio, and M. Karin. 1995. Phosphorylation of IκB precedes but is not sufficient for its dissociation from NF-κB. Mol. Cell. Biol. 15: 1302-1311.
18. Donald, R., D.W. Ballard, and J. Hawiger. 1995. Proteolytic processing of NF-κB/IκB in human monocytes. J. Biol. Chem. 270: 9-12.
19. Ernst, M.K., L.L. Dunn, and N.R. Rice. 1995. The PEST-like sequence of IκBα is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA homodimers. Mol. Cell. Biol. 15: 872-882.
20. Eytan, E., T. Armon, H. Heller, S. Beck, and A. Hershko. 1993. Ubiquitin C-terminal hydrolase activity associated with the 26S protease complex. J. Biol. Chem. 268: 4668-4674.
21. Fan, C.-M. and T. Maniatis. 1991. Generation of p50 subunit of NF-κB by processing of p105 through an ATP-dependent pathway. Nature 354: 395-398.
22. Fenteany, G., R.F. Standaert, W.S. Lane, S. Choi, E.J. Corey, and S.L. Schreiber. 1995. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 268: 726-731.
23. Finco, T.S., A.A. Beg, and A.S. Baldwin Jr. 1994. Inducible phosphorylation of IκBα is not sufficient for its dissociation from NF-κB and is inhibited by protease inhibitors. Proc. Natl. Acad. Sci. 91: 11884-11888.
24. Ganchi, P.A., S.-C. Sun, W.C. Greene, and D.W. Ballard. 1992. IκB/MAD-3 masks the nuclear localization signal of NF-κB p65 and requires the trans-activation domain to inhibit NF-κB p65 DNA binding. Mol. Biol. Cell 3: 1339-1352.
25. Ganoth, D., E. Leshinsky, E. Eytan, and A. Hershko. 1988. A multicomponent system that degrades proteins conjugated to ubiquitin. J. Biol. Chem. 263: 12412-12419.
26. Ghosh, G., G. Van Duyne, S. Ghosh, and P.B. Sigler. 1995. Structure of NF-κB p50 homodimer bound to a κB site. Nature 373: 303-310.
27. Gilmore, T.D. and P.J. Morin. 1993. The IκB proteins: Members of a multifunctional family. Trends Genet. 9: 427-433.
28. Glotzer, M., A.W. Murray, and M.W. Kirschner. 1991. Cyclin is degraded by the ubiquitin pathway. Nature 349: 132-138.
29. Goldberg, A.L. 1992. The mechanism and functions of ATP-dependent proteases in bacterial and animal cells. Eur. J. Biochem. 203: 9-23.
30. Grilli, M., J.J.-S. Chiu, and M.J. Lenardo. 1993. NF-κB and Rel: Participants in a multiform transcriptional regulatory system. Int. Rev. Cytol. 143: 1-62.
31. Haas, A.L. and P.M. Bright. 1985. The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J. Biol. Chem. 250: 12464-12473.
32. Henkel, T., U. Zabel, K. van Zee, J.M. Muller, E. Fanning, and P. Baeuerle. 1992. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-κB subunit. Cell 68: 1121-1133.
33. Henkel, T., T. Machleidt, I. Alkalay, M. Kronke, Y. Ben-Neriah, and P.A. Baeuerle. 1993. Rapid proteolysis of IκB-α is necessary in the activation of transcription factor NF-κB. Nature 365: 182-185.
34. Hershko, A. and A. Ciechanover. 1992. The ubiquitin system for protein degradation. Annu. Rev. Biochem. 61: 761-807.
35. Hershko, A. and H. Heller. 1985. Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Commun. 128: 1079-1086.
36. Hershko, A., D. Ganoth, J. Pehrson, R.E. Palazzo, and L.H. Cohen. 1991. Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. J. Biol. Chem. 266: 16376-16379.
37. Hershko, A., D. Ganoth, V. Sudakin, A. Dahan, L. Cohen, F.C. Luca, J.V. Ruderman, and E. Eytan. 1994. Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2. J. Biol. Chem. 269: 4940-4946.
38. Hochstrasser, M., M.J. Ellison, V. Chau, and A. Varshavsky. 1991. The short-lived MATα2 repressor is ubiquitinated in vivo. Proc. Natl. Acad. Sci. 88: 4606-4610.
39. Hough, R., G. Pratt, and M. Rechsteiner. 1987. Purification of two high molecular weight proteases from rabbit reticulocyte lysate. J. Biol. Chem. 262: 8303-8313.
40. Ishikawa, Y., N. Mukaida, K. Kuno, N. Rice, S. Okamoto, and K. Matsushima. 1995. Establishment of lipopolysaccharide-dependent nuclear factor κB activation in a cell free system. J. Biol. Chem. 270: 4158-4164.
41. Jaffray, E., K.M. Wood, and R.T. Hay. 1995. Domain organization of IκBα and sites of interaction with NF-κB p65. Mol. Cell. Biol. 15: 2166-2172.
42. Jentsch, S. 1992. The ubiquitin-conjugation system. Annu. Rev. Genet. 26: 179-205.
43. Kornitzer, D., B. Raboy, R.G. Kulka, and G.R. Fink. 1994. Regulated degradation of the transcription factor Gcn4. EMBO J. 13: 6021-6030.
44. Lehming, N., S. McGuire, J.M. Brickman, and M. Ptashne. 1995. Mechanism of action of an inhibitor of a rel protein, Proc. Natl. Acad. Sci. (in press).
45. Lin, Y.-C., K. Brown, and U. Siebenlist. 1995. Activation of NF-κB requires proteolysis of the inhibitor IκB-α: Signal-induced phosphorylation of IκB-α alone does not release active NF-κB. Proc. Natl. Acad. Sci. 92: 552-556.
46. Liou, H.-C., G.P. Nolan, S. Ghosh, T. Fujita, and D. Baltimore. 1992. The NF-κB precursor, p105, contains an internal IκB-like inhibitor that preferentially inhibits p50. EMBO J. 11: 3003-3009.
47. Lowe, J. and R.J. Mayer. 1990. Ubiquitin, cell stress and diseases of the nervous system. Neuropathol. Appl. Neurobiol. 16: 281-291.
48. Luca, F.C., E.K. Shibuya, C.E. Dohrmann, and J.V. Ruderman. 1991. Both cyclin AΔ60 and BΔ97 are stable and arrest cells in M-phase, but only cyclin BΔ97 turns on cyclin destruction. EMBO J. 10: 4311-4320.
49. Machleidt, T., K. Wiegmann, T. Henkel, S. Shutze, P. Baeuerle, and M. Kronke. 1994. Sphingomyelinase activates proteolytic IκB-α degradation in a cell-free system. J. Biol. Chem. 269: 13760-13765.
50. Mayer, A.N. and K.D. Wilkinson. 1989. Detection, resolution, and nomenclature of multiple ubiquitin carboxyl-terminal esterases from bovine calf thymus. Biochemistry 28: 166-172.
51. Mellits, K.H., R.T. Hay, and S. Goodbourn. 1993. Proteolytic degradation of MAD3 (IκBα) and enhanced processing of the NF-κB precursor p105 are obligatory steps in the activation of NF-κB. Nucleic Acids Res. 21: 5059-5066.
52. Menon, S.D., S. Qin, G.R. Guy, and Y.H. Tan. 1993. Differential induction of nuclear NF-κB by protein phosphatase inhibitors in primary and transformed human cells. J. Biol. Chem. 268: 26805-26812.
53. Mercurio, F., J.A. DiDonato, C. Rosette, and M. Karin. 1993. P105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction. Genes & Dev. 7: 705-718.
54. Miyamoto, S., M. Maki, M.J. Schmitt, M. Hatanaka, and I.M. Verma. 1994. Tumor necrosis factor α-induced phosphorylation of IκBα is a signal for its degradation but not dissociation from NF-κB. Proc. Natl. Acad. Sci. 91: 12740-12744.
55. Muller, C.W., F.A. Rey, M. Sodeoka, G.L. Verdine, and S.C. Harrison. 1995. Structure of the NF-κB p50 homodimer bound to DNA. Nature 373: 311-317.
56. Naumann, M. and C. Scheidereit. 1994. Activation of NF-κB in vivo is regulated by multiple phosphorylations. EMBO J. 13: 4597-4607.
57. Neumann, M., K. Tsapos, J.A. Scheppler, J. Ross, and B.R. Franza Jr. 1992. Identification of complex formation between two intracellular tyrosine kinase receptor substrates: Human c-Rel and the p105 precursor of p50 NF-κB. Oncogene 7: 2059-2104.
58. Palombella, V.J., O.J. Rando, A.L. Goldberg, and T. Maniatis. 1994. The ubiquitin-proteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB. Cell 78: 773-785.
59. Peters, J.M. 1994. Proteasomes: Protein degradation machines in the cell. Trends Biochem. Sci. 19: 377-382.
60. Read, M.A., A.S. Neish, F.W. Luscinskas, V.J. Palombella, T. Maniatis, and T. Collins. 1995. The proteasome pathway is required for cytokine-induced endothelial leukocyte adhesion molecule expression. Immunity 2: 1-20.
61. Rechsteiner, M., L. Hoffman, and W. Dubiel. 1993. The multicatalytic and 26S proteases. J. Biol. Chem. 268: 6065-6068.
62. Rice, N.R. and M.K. Ernst. 1993. In vivo control of NF-κB activation by IκB-α. EMBO J. 12: 4685-4695.
63. Rice, N.R., M.L. MacKichan, and A. Israel. 1992. The precursor of NF-κB p50 has IκB-like functions. Cell 71: 243-253.
64. Rock, K.L., C. Gramm, L. Rothstein, K. Clark, R. Stein, L. Dick, D. Hwang, and A.L. Goldberg. 1994. Inhibitors of the proteasome block degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78: 761-771.
65. Rogers, S., R. Wells, and M. Rechsteiner. 1986. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 234: 364-368.
66. Scheffner, M., J.M. Huibregtse, R.D. Vierstra, and P.M. Howley. 1993. The HPV-16 E6 and E6AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75: 495-505.
67. Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NF-κB. Annu. Rev. Cell. Biol. 10: 405-455.
68. Sun, S.-C., P.A. Ganchi, D.W. Ballard, and W.D. Greene. 1993. NF-κB controls expression of inhibitor IκB-α: Evidence for an inducible autoregulatory pathway. Science 259: 1912-1915.
69. Sun, S.-C., P.A. Ganchi, C. Beraud, D.W. Ballard, and W.C. Greene. 1994a. Autoregulation of the NF-κB transactivator ReIA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc. Natl. Acad. Sci. 91: 1346-1350.
70. Sun, S.-C., J. Elwood, C. Beraud, and W.C. Greene. 1994b. Human T-cell leukemia virus type I tax activation of NF-κB/ Rel involves phosphorylation and degradation of IκBα and RelA (p65)-mediated induction of the c-rel gene. Mol. Cell. Biol. 14: 7377-7384.
71. Thanos, D. and T. Maniatis. 1995. NF-κB: A lesson in family values. Cell 80: 529-532.
72. Thevenin, C., S.-C. Kim, P. Rieckmann, H. Fujiki, M.A. Norcross, M.B. Sporn, A.S. Fauci, and J.H. Kehrl. 1990. Induction of nuclear factor-κB and the human immunodeficiency virus long terminal repeat by okadaic acid, a specific inhibitor of phosphatases 1 and 2A. New Biol. 2: 793-800.
73. 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.
74. Traenckner, E.B.-M., S. Wilk, and P.A. Baeuerle. 1994. A proteasome inhibitor prevents activation of NF-κB and stabilizes a newly phosphorylated form of IκB-α that is still bound to NF-κB. EMBO J. 13: 5433-5441.
75. Treier, M., L.M. Staszewski, and D. Bohmann. 1994. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the δ domain. Cell 78: 787-798.
76. cdc28-mediated control of cln3 cyclin degradation. Mol. Cell. Biol. 15: 731-741.
77. Zabel, U., T. Henkel, M. dos Santos Silva, and P. Baeuerle. 1993. Nuclear uptake control of NF-κB by MAD-3 and IκB protein present in the nucleus. EMBO J. 12: 201-211.