This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rodriguez, M. S.
Right arrow Articles by Hay, R. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodriguez, M. S.
Right arrow Articles by Hay, R. T.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 05 1995, 2413-2419, Vol 15, No. 5
Copyright © 1995, American Society for Microbiology

Inducible degradation of I kappa B alpha in vitro and in vivo requires the acidic C-terminal domain of the protein

MS Rodriguez, I Michalopoulos, F Arenzana-Seisdedos and RT Hay
Unite d'Immunologie Virale, Institut Pasteur, Paris, France.

After exposure of cells to tumor necrosis factor (TNF), I kappa B alpha is rapidly degraded by a proteolytic activity that is required for nuclear localization and activation of transcription factor NF-kappa B. To investigate this problem, we have developed a cell-free system to study the degradation of I kappa B alpha initiated in vivo. In this in vitro system, characteristics of endogenous I kappa B alpha degradation were comparable to those observed in vivo. Recombinant I kappa B alpha, when added to lysates from cells exposed to TNF, was specifically degraded by a cellular proteolytic activity; however, it was stable in extracts from unstimulated cells. Inhibition characteristics of the proteolytic activity responsible for I kappa B alpha degradation suggest the involvement of a serine protease. Analysis of mutated forms of I kappa B alpha in the in vitro system demonstrated that an I kappa B alpha species which was unable to interact with NF-kappa B was still efficiently degraded. In contrast, deletion of the C-terminal 61 amino acids from I kappa B alpha rendered the protein resistant to proteolytic degradation. Expression of I kappa B alpha mutated forms in COS-7 cells confirmed the importance of the C-terminal domain for the degradation of the protein in vivo following cell activation. Thus, it is likely that the acidic, negatively charged region represented by the C-terminal 61 amino acids of the protein contains residues critical for TNF-inducible degradation of I kappa B alpha.


This article has been cited by other articles:

  • Daskalogianni, C., Apcher, S., Candeias, M. M., Naski, N., Calvo, F., Fahraeus, R. (2008). Gly-Ala Repeats Induce Position- and Substrate-specific Regulation of 26 S Proteasome-dependent Partial Processing. J. Biol. Chem. 283: 30090-30100 [Abstract] [Full Text]  
  • Kumagai, H., Hakoyama, T., Umehara, Y., Sato, S., Kaneko, T., Tabata, S., Kouchi, H. (2007). A Novel Ankyrin-Repeat Membrane Protein, IGN1, Is Required for Persistence of Nitrogen-Fixing Symbiosis in Root Nodules of Lotus japonicus. Plant Physiol. 143: 1293-1305 [Abstract] [Full Text]  
  • Ganguli, A., Persson, L., Palmer, I. R., Evans, I., Yang, L., Smallwood, R., Black, R., Qwarnstrom, E. E. (2005). Distinct NF-{kappa}B Regulation by Shear Stress Through Ras-Dependent I{kappa}B{alpha} Oscillations: Real-Time Analysis of Flow-Mediated Activation in Live Cells. Circ. Res. 96: 626-634 [Abstract] [Full Text]  
  • Yang, L., Ross, K., Qwarnstrom, E. E. (2003). RelA Control of I{kappa}B{alpha} Phosphorylation: A POSITIVE FEEDBACK LOOP FOR HIGH AFFINITY NF-{kappa}B COMPLEXES. J. Biol. Chem. 278: 30881-30888 [Abstract] [Full Text]  
  • Bierhaus, A., Schiekofer, S., Schwaninger, M., Andrassy, M., Humpert, P. M., Chen, J., Hong, M., Luther, T., Henle, T., Kloting, I., Morcos, M., Hofmann, M., Tritschler, H., Weigle, B., Kasper, M., Smith, M., Perry, G., Schmidt, A.-M., Stern, D. M., Haring, H.-U., Schleicher, E., Nawroth, P. P. (2001). Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-{kappa}B. Diabetes 50: 2792-2808 [Abstract] [Full Text]  
  • Baetu, T. M., Kwon, H., Sharma, S., Grandvaux, N., Hiscott, J. (2001). Disruption of NF-{kappa}B Signaling Reveals a Novel Role for NF-{kappa}B in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression. J. Immunol. 167: 3164-3173 [Abstract] [Full Text]  
  • Yang, J., Richmond, A. (2001). Constitutive I{{kappa}}B Kinase Activity Correlates with Nuclear Factor-{{kappa}}B Activation in Human Melanoma Cells. Cancer Res. 61: 4901-4909 [Abstract] [Full Text]  
  • Hay, D. C., Kemp, G. D., Dargemont, C., Hay, R. T. (2001). Interaction between hnRNPA1 and I{kappa}B{alpha} Is Required for Maximal Activation of NF-{kappa}B-Dependent Transcription. Mol. Cell. Biol. 21: 3482-3490 [Abstract] [Full Text]  
  • Rodriguez, M. S., Desterro, J. M. P., Lain, S., Lane, D. P., Hay, R. T. (2000). Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation. Mol. Cell. Biol. 20: 8458-8467 [Abstract] [Full Text]  
  • Chen, C.-L., Singh, N., Yull, F. E., Strayhorn, D., Van Kaer, L., Kerr, L. D. (2000). Lymphocytes Lacking I{kappa}B-{alpha} Develop Normally, But Have Selective Defects in Proliferation and Function. J. Immunol. 165: 5418-5427 [Abstract] [Full Text]  
  • Carlotti, F., Chapman, R., Dower, S. K., Qwarnstrom, E. E. (1999). Activation of Nuclear Factor kappa B in Single Living Cells. DEPENDENCE OF NUCLEAR TRANSLOCATION AND ANTI-APOPTOTIC FUNCTION ON EGFPRELA CONCENTRATION. J. Biol. Chem. 274: 37941-37949 [Abstract] [Full Text]  
  • Rothwarf, D. M., Karin, M. (1999). The NF-{kappa}B Activation Pathway: A Paradigm in Information Transfer from Membrane to Nucleus. Sci Signal 1999: re1-re1 [Abstract] [Full Text]  
  • Shumway, S. D., Maki, M., Miyamoto, S. (1999). The PEST Domain of Ikappa Balpha Is Necessary and Sufficient for in Vitro Degradation by {micro}-Calpain. J. Biol. Chem. 274: 30874-30881 [Abstract] [Full Text]  
  • Algarte, M., Kwon, H., Genin, P., Hiscott, J. (1999). Identification by In Vivo Genomic Footprinting of a Transcriptional Switch Containing NF-kappa B and Sp1 That Regulates the Ikappa Balpha Promoter. Mol. Cell. Biol. 19: 6140-6153 [Abstract] [Full Text]  
  • Weil, R., Sirma, H., Giannini, C., Kremsdorf, D., Bessia, C., Dargemont, C., Brechot, C., Israel, A. (1999). Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-kappa B Inhibitor Ikappa Balpha. Mol. Cell. Biol. 19: 6345-6354 [Abstract] [Full Text]  
  • Uehara, T., Matsuno, J., Kaneko, M., Nishiya, T., Fujimuro, M., Yokosawa, H., Nomura, Y. (1999). Transient Nuclear Factor kappa B (NF-kappa B) Activation Stimulated by Interleukin-1beta May Be Partly Dependent on Proteasome Activity, but Not Phosphorylation and Ubiquitination of the Ikappa Balpha Molecule, in C6 Glioma Cells. REGULATION OF NF-kappa B LINKED TO CHEMOKINE PRODUCTION. J. Biol. Chem. 274: 15875-15882 [Abstract] [Full Text]  
  • Algarté, M., Nguyen, H., Heylbroeck, C., Lin, R., Hiscott, J. (1999). Ikappa B-Mediated Inhibition of Virus-Induced Beta Interferon Transcription. J. Virol. 73: 2694-2702 [Abstract] [Full Text]  
  • Turpin, P., Hay, R. T., Dargemont, C. (1999). Characterization of Ikappa Balpha Nuclear Import Pathway. J. Biol. Chem. 274: 6804-6812 [Abstract] [Full Text]  
  • Chen, E., Hrdlickova, R., Nehyba, J., Longo, D. L., Bose Jr., H. R., Li, C.-C. H. (1998). Degradation of Proto-oncoprotein c-Rel by the Ubiquitin-Proteasome Pathway. J. Biol. Chem. 273: 35201-35207 [Abstract] [Full Text]  
  • Liu, L., Kwak, Y.-T., Bex, F., García-Martínez, L. F., Li, X.-H., Meek, K., Lane, W. S., Gaynor, R. B. (1998). DNA-Dependent Protein Kinase Phosphorylation of Ikappa Balpha and Ikappa Bbeta Regulates NF-kappa B DNA Binding Properties. Mol. Cell. Biol. 18: 4221-4234 [Abstract] [Full Text]  
  • Kwon, H., Pelletier, N., DeLuca, C., Genin, P., Cisternas, S., Lin, R., Wainberg, M. A., Hiscott, J. (1998). Inducible Expression of Ikappa Balpha Repressor Mutants Interferes with NF-kappa B Activity and HIV-1 Replication in Jurkat T Cells. J. Biol. Chem. 273: 7431-7440 [Abstract] [Full Text]  
  • Revilla, Y., Callejo, M., Rodriguez, J. M., Culebras, E., Nogal, M. L., Salas, M. L., Vinuela, E., Fresno, M. (1998). Inhibition of Nuclear Factor kappa B Activation by a Virus-encoded Ikappa B-like Protein. J. Biol. Chem. 273: 5405-5411 [Abstract] [Full Text]  
  • Hiramoto, M., Shimizu, N., Sugimoto, K., Tang, J., Kawakami, Y., Ito, M., Aizawa, S., Tanaka, H., Makino, I., Handa, H. (1998). Nuclear Targeted Suppression of NF-{kappa}B Activity by the Novel Quinone Derivative E3330. J. Immunol. 160: 810-819 [Abstract] [Full Text]  
  • Palmer, G. H., Machado, J. Jr., Fernandez, P., Heussler, V., Perinat, T., Dobbelaere, D. A. E. (1997). Parasite-mediated nuclear factor kappa B regulation in lymphoproliferation caused by Theileria parva infection. Proc. Natl. Acad. Sci. USA 94: 12527-12532 [Abstract] [Full Text]  
  • Tashiro, K., Pando, M. P., Kanegae, Y., Wamsley, P. M., Inoue, S., Verma, I. M. (1997). Direct involvement of the ubiquitin-conjugating enzyme Ubc9/Hus5 in the degradation of Ikappa Balpha. Proc. Natl. Acad. Sci. USA 94: 7862-7867 [Abstract] [Full Text]  
  • Weil, R., Laurent-Winter, C., Israel, A. (1997). Regulation of Ikappa Bbeta Degradation. SIMILARITIES TO AND DIFFERENCES FROM Ikappa Balpha. J. Biol. Chem. 272: 9942-9949 [Abstract] [Full Text]  
  • Bachelerie, F, Rodriguez, M., Dargemont, C, Rousset, D, Thomas, D, Virelizier, J., Arenzana-Seisdedos, F (1997). Nuclear export signal of IkappaBalpha interferes with the Rev-dependent posttranscriptional regulation of human immunodeficiency virus type I. J. Cell Sci. 110: 2883-2893 [Abstract]  
  • Arenzana-Seisdedos, F, Turpin, P, Rodriguez, M, Thomas, D, Hay, R., Virelizier, J., Dargemont, C (1997). Nuclear localization of I kappa B alpha promotes active transport of NF-kappa B from the nucleus to the cytoplasm. J. Cell Sci. 110: 369-378 [Abstract]  
  • Beauparlant, P., Lin, R., Hiscott, J. (1996). The Role of the C-terminal Domain of IkappaBalpha in Protein Degradation and Stabilization. J. Biol. Chem. 271: 10690-10696 [Abstract] [Full Text]  
  • Roff, M., Thompson, J., Rodriguez, M. S., Jacque, J.-M., Baleux, F., Arenzana-Seisdedos, F., Hay, R. T. (1996). Role of IkappaBalpha Ubiquitination in Signal-induced Activation of NF-kappaB in Vivo. J. Biol. Chem. 271: 7844-7850 [Abstract] [Full Text]  
  • MacKichan, M. L., Logeat, F.édér., Israël, A. (1996). Phosphorylation of p105 PEST Sequences via a Redox-insensitive Pathway Up-regulates Processing to p50 NF-kappaB. J. Biol. Chem. 271: 6084-6091 [Abstract] [Full Text]  
  • Kuno, K., Ishikawa, Y., Ernst, M. K., Ogata, M., Rice, N. R., Mukaida, N., Matsushima, K. (1995). Identification of an IkappaBalpha-associated Protein Kinase in a Human Monocytic Cell Line and Determination of Its Phosphorylation Sites on IkappaBalpha. J. Biol. Chem. 270: 27914-27919 [Abstract] [Full Text]  
  • Verma, I M, Stevenson, J K, Schwarz, E M, Van Antwerp, D, Miyamoto, S (1995). Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.. Genes Dev. 9: 2723-2735  
  • Schwamborn, K., Weil, R., Courtois, G., Whiteside, S. T., Israel, A. (2000). Phorbol Esters and Cytokines Regulate the Expression of the NEMO-related Protein, a Molecule Involved in a NF-kappa B-independent Pathway. J. Biol. Chem. 275: 22780-22789 [Abstract] [Full Text]  
  • Pando, M. P., Verma, I. M. (2000). Signal-dependent and -independent Degradation of Free and NF-kappa B-bound Ikappa Balpha. J. Biol. Chem. 275: 21278-21286 [Abstract] [Full Text]  
  • Caunt, C. J., Kiss-Toth, E., Carlotti, F., Chapman, R., Qwarnstrom, E. E. (2001). Ras Controls Tumor Necrosis Factor Receptor-associated Factor (TRAF)6-dependent Induction of Nuclear Factor-kappa B. SELECTIVE REGULATION THROUGH RECEPTOR SIGNALING COMPONENTS. J. Biol. Chem. 276: 6280-6288 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»