This Article
Right arrow Full Text
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 Miyamoto, S.
Right arrow Articles by Shumway, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miyamoto, S.
Right arrow Articles by Shumway, S. D.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Jan 1998, 19-29, Vol 18, No. 1
Copyright © 1998, American Society for Microbiology

Novel IkappaB alpha proteolytic pathway in WEHI231 immature B cells

S Miyamoto, BJ Seufzer and SD Shumway
Department of Human Oncology, University of Wisconsin-Madison, 53792, USA. miyamoto@humonc.wisc.edu

The Rel/NF-kappaB family of transcription factors is sequestered in the cytoplasm of most mammalian cells by inhibitor proteins belonging to the IkappaB family. Degradation of IkappaB by a phosphorylation- dependent ubiquitin-proteasome (inducible) pathway is believed to allow nuclear transport of active Rel/NF-kappaB dimers. Rel/NF-kappaB (a p50- c-Rel dimer) is constitutively nuclear in murine B cells, such as WEHI231 cells. In these cells, p50, c-Rel, and IkappaB alpha are synthesized at high levels but only IkappaB alpha is rapidly degraded. We have examined the mechanism of IkappaB alpha degradation and its relation to constitutive p50-c-Rel activation. We demonstrate that all IkappaB alpha is found complexed with c-Rel protein in the cytoplasm. Additionally, rapid IkappaB alpha proteolysis is independent of but coexistent with the inducible pathway and can be inhibited by calcium chelators and some calpain inhibitors. Conditions that prevent degradation of IkappaB alpha also inhibit nuclear p50-c-Rel activity. Furthermore, the half-life of nuclear c-Rel is much shorter than that of the cytoplasmic form, underscoring the necessity for its continuous nuclear transport to maintain constitutive p50-c-Rel activity. We observed that IkappaB beta, another NF-kappaB inhibitor, is also complexed with c-Rel but slowly degraded by a proteasome-dependent process in WEHI231 cells. In addition, IkappaB beta is basally phosphorylated and cytoplasmic. We thus suggest that calcium-dependent IkappaB alpha proteolysis maintains nuclear transport of a p50-c-Rel heterodimer which in turn activates the synthesis of IkappaB alpha, p50, and c-Rel to sustain this dynamic process in WEHI231 B cells.


This article has been cited by other articles:

  • Fukuyo, Y., Kitamura, T., Inoue, M., Horikoshi, N. T., Higashikubo, R., Hunt, C. R., Usheva, A., Horikoshi, N. (2009). Phosphorylation-Dependent Lys63-Linked Polyubiquitination of Daxx Is Essential for Sustained TNF-{alpha}-Induced ASK1 Activation. Cancer Res. 69: 7512-7517 [Abstract] [Full Text]  
  • Chae, J. J., Wood, G., Richard, K., Jaffe, H., Colburn, N. T., Masters, S. L., Gumucio, D. L., Shoham, N. G., Kastner, D. L. (2008). The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-{kappa}B through its N-terminal fragment. Blood 112: 1794-1803 [Abstract] [Full Text]  
  • Biswas, G., Tang, W., Sondheimer, N., Guha, M., Bansal, S., Avadhani, N. G. (2008). A Distinctive Physiological Role for I{kappa}B{beta} in the Propagation of Mitochondrial Respiratory Stress Signaling. J. Biol. Chem. 283: 12586-12594 [Abstract] [Full Text]  
  • Sethi, G., Sung, B., Aggarwal, B. B. (2008). Nuclear Factor-{kappa}B Activation: From Bench to Bedside. Exp. Biol. Med. 233: 21-31 [Abstract] [Full Text]  
  • Souvannavong, V., Saidji, N., Chaby, R. (2007). Lipopolysaccharide from Salmonella enterica Activates NF-{kappa}B through both Classical and Alternative Pathways in Primary B Lymphocytes. Infect. Immun. 75: 4998-5003 [Abstract] [Full Text]  
  • Ashworth, T., Roy, A. L. (2007). Cutting Edge: TFII-I Controls B Cell Proliferation via Regulating NF-{kappa}B. J. Immunol. 178: 2631-2635 [Abstract] [Full Text]  
  • Majdalawieh, A., Zhang, L., Ro, H.-S. (2007). Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-{kappa}B via I{kappa}B{alpha} Negative Regulation. Mol. Biol. Cell 18: 930-942 [Abstract] [Full Text]  
  • Pani, B., Cornatzer, E., Cornatzer, W., Shin, D.-M., Pittelkow, M. R., Hovnanian, A., Ambudkar, I. S., Singh, B. B. (2006). Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease. Mol. Biol. Cell 17: 4446-4458 [Abstract] [Full Text]  
  • Vigorito, E., Gambardella, L., Colucci, F., McAdam, S., Turner, M. (2005). Vav proteins regulate peripheral B-cell survival. Blood 106: 2391-2398 [Abstract] [Full Text]  
  • Berchtold, C. M., Chen, K.-S., Miyamoto, S., Gould, M. N. (2005). Perillyl Alcohol Inhibits a Calcium-Dependent Constitutive Nuclear Factor-{kappa}B Pathway. Cancer Res. 65: 8558-8566 [Abstract] [Full Text]  
  • Valley, C. C., Metivier, R., Solodin, N. M., Fowler, A. M., Mashek, M. T., Hill, L., Alarid, E. T. (2005). Differential Regulation of Estrogen-Inducible Proteolysis and Transcription by the Estrogen Receptor {alpha} N Terminus. Mol. Cell. Biol. 25: 5417-5428 [Abstract] [Full Text]  
  • Wuerzberger-Davis, S. M., Chang, P.-Y., Berchtold, C., Miyamoto, S. (2005). Enhanced G2-M Arrest by Nuclear Factor-{kappa}B-Dependent p21waf1/cip1 Induction. Mol Cancer Res 3: 345-353 [Abstract] [Full Text]  
  • Doerre, S., Mesires, K. P., Daley, K. M., McCarty, T., Knoetig, S., Corley, R. B. (2005). Reductions in I{kappa}B{epsilon} and Changes in NF-{kappa}B Activity during B Lymphocyte Differentiation. J. Immunol. 174: 983-991 [Abstract] [Full Text]  
  • O'Connor, S., Shumway, S., Miyamoto, S. (2005). Inhibition of I{kappa}B{alpha} Nuclear Export as an Approach to Abrogate Nuclear Factor-{kappa}B-Dependent Cancer Cell Survival. Mol Cancer Res 3: 42-49 [Abstract] [Full Text]  
  • O'Connor, S., Shumway, S. D., Amanna, I. J., Hayes, C. E., Miyamoto, S. (2004). Regulation of Constitutive p50/c-Rel Activity via Proteasome Inhibitor-Resistant I{kappa}B{alpha} Degradation in B Cells. Mol. Cell. Biol. 24: 4895-4908 [Abstract] [Full Text]  
  • Aleyasin, H., Cregan, S. P., Iyirhiaro, G., O'Hare, M. J., Callaghan, S. M., Slack, R. S., Park, D. S. (2004). Nuclear Factor-{kappa}B Modulates the p53 Response in Neurons Exposed to DNA Damage. J. Neurosci. 24: 2963-2973 [Abstract] [Full Text]  
  • Nemeth, Z. H., Wong, H. R., Odoms, K., Deitch, E. A., Szabo, C., Vizi, E. S., Hasko, G. (2004). Proteasome Inhibitors Induce Inhibitory {kappa}B (I{kappa}B) Kinase Activation, I{kappa}B{alpha} Degradation, and Nuclear Factor {kappa}B Activation in HT-29 Cells. Mol. Pharmacol. 65: 342-349 [Abstract] [Full Text]  
  • FOWLER, A. M., SOLODIN, N., PREISLER-MASHEK, M. T., ZHANG, P., LEE, A. V., ALARID, E. T. (2004). Increases in estrogen receptor-{alpha} concentration in breast cancer cells promote serine 118/104/106-independent AF-1 transactivation and growth in the absence of estrogen. FASEB J. 18: 81-93 [Abstract] [Full Text]  
  • Waris, G., Livolsi, A., Imbert, V., Peyron, J.-F., Siddiqui, A. (2003). Hepatitis C Virus NS5A and Subgenomic Replicon Activate NF-{kappa}B via Tyrosine Phosphorylation of I{kappa}B{alpha} and Its Degradation by Calpain Protease. J. Biol. Chem. 278: 40778-40787 [Abstract] [Full Text]  
  • De Bosscher, K., Vanden Berghe, W., Haegeman, G. (2003). The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression. Endocr. Rev. 24: 488-522 [Abstract] [Full Text]  
  • Gern, J. E., French, D. A., Grindle, K. A., Brockman-Schneider, R. A., Konno, S.-I., Busse, W. W. (2003). Double-Stranded RNA Induces the Synthesis of Specific Chemokines by Bronchial Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 28: 731-737 [Abstract] [Full Text]  
  • Bernal-Mizrachi, E., Wen, W., Shornick, M., Permutt, M. A. (2002). Activation of Nuclear Factor-{kappa}B by Depolarization and Ca2+ Influx in MIN6 Insulinoma Cells. Diabetes 51: S484-488 [Abstract] [Full Text]  
  • Romieu-Mourez, R., Landesman-Bollag, E., Seldin, D. C., Sonenshein, G. E. (2002). Protein Kinase CK2 Promotes Aberrant Activation of Nuclear Factor-{kappa}B, Transformed Phenotype, and Survival of Breast Cancer Cells. Cancer Res. 62: 6770-6778 [Abstract] [Full Text]  
  • Li, G., Iyengar, R. (2002). Calpain as an effector of the Gq signaling pathway for inhibition of Wnt/beta -catenin-regulated cell proliferation. Proc. Natl. Acad. Sci. USA 99: 13254-13259 [Abstract] [Full Text]  
  • Huang, T. T., Feinberg, S. L., Suryanarayanan, S., Miyamoto, S. (2002). The Zinc Finger Domain of NEMO Is Selectively Required for NF-{kappa}B Activation by UV Radiation and Topoisomerase Inhibitors. Mol. Cell. Biol. 22: 5813-5825 [Abstract] [Full Text]  
  • Witkowski, J. M., Zmuda-Trzebiatowska, E., Swiercz, J. M., Cichorek, M., Ciepluch, H., Lewandowski, K., Bryl, E., Hellmann, A. (2002). Modulation of the activity of calcium-activated neutral proteases (calpains) in chronic lymphocytic leukemia (B-CLL) cells. Blood 100: 1802-1809 [Abstract] [Full Text]  
  • Chu, J., Jeffries, S., Norton, J. E., Capobianco, A. J., Bresnick, E. H. (2002). Repression of Activator Protein-1-mediated Transcriptional Activation by the Notch-1 Intracellular Domain. J. Biol. Chem. 277: 7587-7597 [Abstract] [Full Text]  
  • Gasparian, A. V., Yao, Y. J., Kowalczyk, D., Lyakh, L. A., Karseladze, A., Slaga, T. J., Budunova, I. V. (2002). The role of IKK in constitutive activation of NF-{kappa}B transcription factor in prostate carcinoma cells. J. Cell Sci. 115: 141-151 [Abstract] [Full Text]  
  • Shumway, S. D., Berchtold, C. M., Gould, M. N., Miyamoto, S. (2002). Evidence for Unique Calmodulin-Dependent Nuclear Factor-kappa B Regulation in WEHI-231 B Cells. Mol. Pharmacol. 61: 177-185 [Abstract] [Full Text]  
  • Shen, J., Channavajhala, P., Seldin, D. C., Sonenshein, G. E. (2001). Phosphorylation by the Protein Kinase CK2 Promotes Calpain-Mediated Degradation of I{kappa}B{alpha}. J. Immunol. 167: 4919-4925 [Abstract] [Full Text]  
  • Tsuji, S., Okamoto, M., Yamada, K., Okamoto, N., Goitsuka, R., Arnold, R., Kiefer, F., Kitamura, D. (2001). B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1. JEM 194: 529-540 [Abstract] [Full Text]  
  • Huang, T. T., Miyamoto, S. (2001). Postrepression Activation of NF-{kappa}B Requires the Amino-Terminal Nuclear Export Signal Specific to I{kappa}B{alpha}. Mol. Cell. Biol. 21: 4737-4747 [Abstract] [Full Text]  
  • Tam, W. F., Wang, W., Sen, R. (2001). Cell-Specific Association and Shuttling of I{kappa}B{alpha} Provides a Mechanism for Nuclear NF-{kappa}B in B Lymphocytes. Mol. Cell. Biol. 21: 4837-4846 [Abstract] [Full Text]  
  • Stramer, B. M., Cook, J. R., Fini, M. E., Taylor, A., Obin, M. (2001). Induction of the Ubiquitin-Proteasome Pathway during the Keratocyte Transition to the Repair Fibroblast Phenotype. IOVS 42: 1698-1706 [Abstract] [Full Text]  
  • Jaspers, I., Zhang, W., Fraser, A., Samet, J. M., Reed, W. (2001). Hydrogen Peroxide Has Opposing Effects on IKK Activity and Ikappa Balpha Breakdown in Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 24: 769-777 [Abstract] [Full Text]  
  • Romieu-Mourez, R., Landesman-Bollag, E., Seldin, D. C., Traish, A. M., Mercurio, F., Sonenshein, G. E. (2001). Roles of IKK Kinases and Protein Kinase CK2 in Activation of Nuclear Factor-{{kappa}}B in Breast Cancer. Cancer Res. 61: 3810-3818 [Abstract] [Full Text]  
  • Pennington, K. N., Taylor, J. A., Bren, G. D., Paya, C. V. (2001). I{kappa}B Kinase-Dependent Chronic Activation of NF-{kappa}B Is Necessary for p21WAF1/Cip1 Inhibition of Differentiation-Induced Apoptosis of Monocytes. Mol. Cell. Biol. 21: 1930-1941 [Abstract] [Full Text]  
  • Chen, F., Demers, L. M., Vallyathan, V., Lu, Y., Castranova, V., Shi, X. (2000). Impairment of NF-kappa B activation and modulation of gene expression by calpastatin. Am. J. Physiol. Cell Physiol. 279: C709-C716 [Abstract] [Full Text]  
  • Fields, E. R., Seufzer, B. J., Oltz, E. M., Miyamoto, S. (2000). A Switch in Distinct I{kappa}B{alpha} Degradation Mechanisms Mediates Constitutive NF-{kappa}B Activation in Mature B Cells. J. Immunol. 164: 4762-4767 [Abstract] [Full Text]  
  • Schoonbroodt, S., Ferreira, V., Best-Belpomme, M., Boelaert, J. R., Legrand-Poels, S., Korner, M., Piette, J. (2000). Crucial Role of the Amino-Terminal Tyrosine Residue 42 and the Carboxyl-Terminal PEST Domain of I{kappa}B{alpha} in NF-{kappa}B Activation by an Oxidative Stress. J. Immunol. 164: 4292-4300 [Abstract] [Full Text]  
  • Huang, T. T., Wuerzberger-Davis, S. M., Seufzer, B. J., Shumway, S. D., Kurama, T., Boothman, D. A., Miyamoto, S. (2000). NF-kappa B Activation by Camptothecin. A LINKAGE BETWEEN NUCLEAR DNA DAMAGE AND CYTOPLASMIC SIGNALING EVENTS. J. Biol. Chem. 275: 9501-9509 [Abstract] [Full Text]  
  • Huang, T. T., Kudo, N., Yoshida, M., Miyamoto, S. (2000). A nuclear export signal in the N-terminal regulatory domain of Ikappa Balpha controls cytoplasmic localization of inactive NF-kappa B/Ikappa Balpha complexes. Proc. Natl. Acad. Sci. USA 97: 1014-1019 [Abstract] [Full Text]  
  • Xia, Y., Chen, S., Wang, Y., Mackman, N., Ku, G., Lo, D., Feng, L. (1999). RelB Modulation of Ikappa Balpha Stability as a Mechanism of Transcription Suppression of Interleukin-1alpha (IL-1alpha ), IL-1beta , and Tumor Necrosis Factor Alpha in Fibroblasts. Mol. Cell. Biol. 19: 7688-7696 [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]  
  • Doerre, S., Corley, R. B. (1999). Constitutive Nuclear Translocation of NF-{kappa}B in B Cells in the Absence of I{kappa}B Degradation. J. Immunol. 163: 269-277 [Abstract] [Full Text]  
  • Welm, A. L., Timchenko, N. A., Darlington, G. J. (1999). C/EBPalpha Regulates Generation of C/EBPbeta Isoforms through Activation of Specific Proteolytic Cleavage. Mol. Cell. Biol. 19: 1695-1704 [Abstract] [Full Text]  
  • Han, Y., Weinman, S., Boldogh, I., Walker, R. K., Brasier, A. R. (1999). Tumor Necrosis Factor-alpha -inducible Ikappa Balpha Proteolysis Mediated by Cytosolic m-Calpain. A MECHANISM PARALLEL TO THE UBIQUITIN-PROTEASOME PATHWAY FOR NUCLEAR FACTOR-kappa B ACTIVATION. J. Biol. Chem. 274: 787-794 [Abstract] [Full Text]  
  • Cheng, J. D., Ryseck, R.-P., Attar, R. M., Dambach, D., Bravo, R. (1998). Functional Redundancy of the Nuclear Factor {kappa}B Inhibitors I{kappa}B{alpha} and I{kappa}B{beta}. JEM 188: 1055-1062 [Abstract] [Full Text]  
  • Cuervo, A. M., Hu, W., Lim, B., Dice, J. F. (1998). Ikappa B Is a Substrate for a Selective Pathway of Lysosomal Proteolysis. Mol. Biol. Cell 9: 1995-2010 [Abstract] [Full Text]  
  • Lam, L. T., Ronchini, C., Norton, J., Capobianco, A. J., Bresnick, E. H. (2000). Suppression of Erythroid but Not Megakaryocytic Differentiation of Human K562 Erythroleukemic Cells by Notch-1. J. Biol. Chem. 275: 19676-19684 [Abstract] [Full Text]  
  • Kouba, D. J., Nakano, H., Nishiyama, T., Kang, J., Uitto, J., Mauviel, A. (2001). Tumor Necrosis Factor-alpha Induces Distinctive NF-kappa B Signaling within Human Dermal Fibroblasts. J. Biol. Chem. 276: 6214-6224 [Abstract] [Full Text]  
  • Petranka, J., Wright, G., Forbes, R. A., Murphy, E. (2001). Elevated Calcium in Preneoplastic Cells Activates NF-kappa B and Confers Resistance to Apoptosis. J. Biol. Chem. 276: 37102-37108 [Abstract] [Full Text]  
  • Yin, L., Laevsky, G., Giardina, C. (2001). Butyrate Suppression of Colonocyte NF-kappa B Activation and Cellular Proteasome Activity. J. Biol. Chem. 276: 44641-44646 [Abstract] [Full Text]  
  • Preisler-Mashek, M. T., Solodin, N., Stark, B. L., Tyriver, M. K., Alarid, E. T. (2002). Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-alpha. Am. J. Physiol. Endocrinol. Metab. 282: E891-E898 [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»