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Research Article

Mapping of the Inducible IκB Phosphorylation Sites That Signal Its Ubiquitination and Degradation†

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Pages 1295-1304 | Received 17 Nov 1995, Accepted 05 Jan 1996, Published online: 29 Mar 2023

REFERENCES

  • Alessi, D. R., Y. Saito, D. G. Campbell, P. Cohen, G. Sithanandam, U. Rapp, A. Ashworth, C. J. Marshall, and S. Cowley. 1994. Identification of the sites in MAP kinase kinase-1 phosphorylation by p74raf-1. EMBO J. 13:1610–1619.
  • 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.
  • Alkalay, I., A. Yaron, A. Hatzubai, A. Orian, A. Ciechanover, and Y. Ben-Neriah. 1995. Stimulation-dependent IκBα phosphorylation marks the NF-κB inhibitor for degradation via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 92:10599–10603.
  • Baeuerle, P. A. 1991. The inducible transcriptional activator NF-κB: regulation by distinct protein subunits. Biochim. Biophys. Acta 1072:63–80.
  • 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.
  • Beg, A. A., T. S. Finco, P. V. Nantermet, and A. 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.
  • Blank, V., P. Kourilsky, and A. Israel. 1992. NF-κB and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem. Sci. 17:135–140.
  • Boyle, W. J., P. van der Geer, and T. Hunter. 1991. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 201:110–149.
  • 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 IκBα to multiple pathways for NF-κB activation. Mol. Cell. Biol. 15:2809–2818.
  • Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist. 1995. Control of IκBα-proteolysis by site-specific, signal-induced phosphorylation. Science 267:1485–1491.
  • Brown, K., S. Park, T. Kanno, G. Franzoso, and U. Siebenlist. 1993. Mutual regulation of the transcriptional activator NF-κB and its inhibitor, IκBα. Proc. Natl. Acad. Sci. USA 90:2532–2536.
  • 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.
  • Ciechanover, A. 1994. The ubiquitin-proteasome proteolytic pathway. Cell 79:1321.
  • Cordle, S. R., R. Donald, M. A. Read, and J. Hawiger. 1993. Lipopolysac-charide induces phosphorylation of MAD-3 and activation of c-Rel and related NF-κB proteins in human monocytic THP-1 cells. J. Biol. Chem. 268:11803–11810.
  • Devary, Y., C. Rosette, J. A. DiDonato, and M. Karin. 1993. NF-κB activation by ultraviolet light not dependent on a nuclear signal. Science 261:1442–1445.
  • DiDonato, J. A. Unpublished observations.
  • DiDonato, J. A., F. Mercurio, and M. Karin. 1995. Phosphorylation of IκBα precedes but is not sufficient for its dissociation from NF-κB. Mol. Cell. Biol. 15:1302–1311.
  • 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. USA 91:11884–11888.
  • Flotow, H., and P. J. Roach. 1991. Role of acidic residues as substrate determinants for casein kinase I. J. Biol. Chem. 25:3724–3727.
  • Ghosh, S., and D. Baltimore. 1990. Activation in vivo of NF-κB by phosphorylation of its inhibitor IκB. Nature (London) 344:678–682.
  • Gilmore, T. D., and P. J. Morin. 1993. The IκB proteins: members of a multifunctional family. Trends Genet. 9:427–433.
  • Goldberg, A. L. 1992. The mechanism and functions of ATP-dependent proteases in bacterial and animal cells. Eur. J. Biochem. 203:9–23.
  • Goldberg, A. L. 1995. Functions of the proteasome: the lysis at the end of the tunnel. Science 268:522–523.
  • Grilli, M., J. J. Chiu, and M. J. Lenardo. 1993. NF-κB and Rel: participants in a multiform transcriptional regulatory system. Int. Rev. Cytol. 143:1–62.
  • Haas, A. L., and P. M. Bright. 1985. The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J. Biol. Chem. 250:12464–12473.
  • Haskill, S., A. A. Beg, S. M. Tompkins, J. S. Morris, A. D. Yurochko, A. Sampson-Johannes, R. Mondal, P. Ralph, and A. Baldwin, Jr. 1991. Characterization of an immediate-early gene induced in adherent monocytes that encodes IκB-like activity. Cell 65:1281–1289.
  • Helmberg, A., N. Auphan, C. Caelles, and M. Karin. 1995. Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor. EMBO J. 14:452–460.
  • Henkel, T., T. Machleidt, I. Alkalay, M. Kronke, T. Ben-Neriah, and P. A. Baeuerle. 1993. Rapid proteolysis of IκBα is necessary for activation of transcription factor NF-κB. Nature (London) 365:182–185.
  • Hershko, A., and A. Ciechanover. 1992. The ubiquitin system for protein degradation. Annu. Rev. Biochem. 61:761–807.
  • Kemp, B. E., D. J. Graves, E. Benjamini, and E. G. Krebs. 1977. Role of multiple basic residues in determining the substrate specificity of cyclic AMP-dependent protein kinase. J. Biol. Chem. 252:4888–4894.
  • 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.
  • Li, S., and J. M. Sedivy. 1993. Raf-1 protein kinase activates the NF-κB transcription factor by dissociating the cytoplasmic NF-κB-IκB complex. Proc. Natl. Acad. Sci. USA 90:9247–9251.
  • Lin, Y.-C., K. Brown, and U. Siebenlist. 1995. Activation of NFκB requires proteolysis of the inhibitor IκBα: signal-induced phosphorylation of IκBα alone does not release active NF-κB. Proc. Natl. Acad. Sci. USA 92:3003–3009.
  • Liou, H. C., and D. Baltimore. 1993. Regulation of the NF-κB/Rel transcription factor and IκB inhibitor system. Curr. Opin. Cell Biol. 5:477–487.
  • Mellits, K. D., R. T. Hay, and S. Goodbourn. 1993. Proteolytic degradation of MAD-3 (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.
  • Mercurio, F., J. DiDonato, C. Rosette, and M. Karin. 1992. Molecular cloning and characterization of a novel Rel/NFKB family member displays structural and functional homology to NF-κB p50/-105. DNA Cell Biol. 11:523–537.
  • 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.
  • Minden, A., A. Lin, M. McMahon, C. Lange-Carter, B. Dérijard, R. J. Davis, G. L. Johnson, and M. Karin. 1994. Differential activation of ERK and JNK MAP kinases by Raf-1 and MEKK. Science 266:1719–1723.
  • 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. USA 91:12740–12744.
  • Palombella, V. J., O. J. Rando, A. L. Goldberg, and T. Maniatis. 1994. The ubiquitin-proteasome pathway is required for processing the NF-κB precursor and the activation of NF-κB. Cell 78:773–785.
  • Schägger, H., and G. von Jagow. 1987. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal. Biochem. 166:368–379.
  • Sen, R., and D. Baltimore. 1986. Inducibility of the κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47:921–928.
  • Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol. 10:405–455.
  • Thanos, D., and T. Maniatis. 1995. NF-κB: a lesson in family values. Cell 80:529–532.
  • Thompson, J. E., R. J. Philips, H. Erdjument-Bromage, P. Tempst, and S. Ghosh. 1995. IκBβ regulates the persistent response in a biphasic activation of NF-κB. Cell 80:573–582.
  • Traenckner, E. B., H. L. Pahl, T. Henkel, K. N. Schmidt, S. Wilk, and P. A. Baeuerle. 1995. Phosphorylation of human IκBα on serines 32 and 36 controls IκBα proteolysis and NF-κB activation in response to diverse stimuli. EMBO J. 14:2876–2883.
  • 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 IκBα that is still bound to NF-κB. EMBO J. 13:5433–5441.
  • Treier, M., L. M. Staszewski, and D. Bhomann. 1994. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the δ domain. Cell 78:787–798.
  • Tuazon, P. T., and J. A. Traugh. 1991. Casein kinase I and II—multipotential serine protein kinases: structure, function and regulation. Adv. Second Messenger Phosphoprotein Res. 23:123–164.
  • Vinitsky, A., C. Michaud, J. C. Powers, and M. Orlowski. 1992. Inhibition of the chymotrypsin-like activity of the pituitary proteinase complex. Biochemistry 31:9421–9428.
  • Whiteside, 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.
  • Wilson, I. A., H. L. Niman, R. A. Houghten, A. R. Cherenson, M. L. Connolly, and R. A. Lerner. 1984. The structure of an antigenic determinant in a protein. Cell 37:767–778.

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