Cell Growth & Differentiation, Vol 4, Issue 9 731-743, Copyright © 1993 by American Association of Cancer Research

ARTICLES

rel/NF-kappa B nuclear complexes that bind kB sites in the murine c-rel promoter are required for constitutive c-rel transcription in B-cells

RJ Grumont, IB Richardson, C Gaff and S Gerondakis
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.

The c-rel protooncogene, a member of a transcription factor family that includes NF-kappa B, displays a complex pattern of gene expression. To understand the basis of this expression, the regulatory region upstream of the murine c-rel transcription start sites has been cloned and characterized. Transcription of the murine c-rel gene initiates at multiple sites downstream of a GC-rich region conserved in the chicken c-rel promoter. This conserved region contains consensus transcription factor binding sites for SP-1 and NF-kappa B (kB3 site) and is sufficient for basal expression in Jurkat T-cells. In contrast, two additional NF-kappa B-like sites (kB1 and kB2) and an octamer consensus binding site, all located upstream of the conserved region, are required for expression of promoter-reporter gene constructs in the B-cell line I29B. NF-kappa B sites kB1 and kB3 bind p50/65 and p50 homodimers, whereas kB2 binds a distinct complex. The consensus octamer site, although only able to bind Oct1 and Oct2 with low affinity, appears to overlap with a binding site for a novel protein(s) expressed in I29B cells. Cotransfection studies show that p75-c-rel and a carboxyl-terminal truncated c-rel protein that lacks the known trans-activating domain both up-regulate the c-rel promoter in I29B cells via a mechanism independent of the NF-kappa B motifs, whereas a mutant c-rel protein lacking the DNA binding domain has no effect. Together, these findings suggest that, in this B-cell line, trans-activation of the c-rel promoter by rel proteins is via an indirect mechanism.

This article has been cited by other articles:

				J. C. Nolz, M. E. Fernandez-Zapico, and D. D. Billadeau TCR/CD28-Stimulated Actin Dynamics Are Required for NFAT1-Mediated Transcription of c-rel Leading to CD28 Response Element Activation J. Immunol., July 15, 2007; 179(2): 1104 - 1112. [Abstract] [Full Text] [PDF]

				M. W. Hansberger, J. A. Campbell, P. Danthi, P. Arrate, K. N. Pennington, K. B. Marcu, D. W. Ballard, and T. S. Dermody I{kappa}B Kinase Subunits {alpha} and {gamma} Are Required for Activation of NF-{kappa}B and Induction of Apoptosis by Mammalian Reovirus J. Virol., February 1, 2007; 81(3): 1360 - 1371. [Abstract] [Full Text] [PDF]

				P.-Y. Chang and S. Miyamoto Nuclear Factor-{kappa}B Dimer Exchange Promotes a p21waf1/cip1 Superinduction Response in Human T Leukemic Cells Mol. Cancer Res., February 1, 2006; 4(2): 101 - 112. [Abstract] [Full Text] [PDF]

				E. Vigorito, L. Gambardella, F. Colucci, S. McAdam, and M. Turner Vav proteins regulate peripheral B-cell survival Blood, October 1, 2005; 106(7): 2391 - 2398. [Abstract] [Full Text] [PDF]

				S. Doerre, K. P. Mesires, K. M. Daley, T. McCarty, S. Knoetig, and R. B. Corley Reductions in I{kappa}B{epsilon} and Changes in NF-{kappa}B Activity during B Lymphocyte Differentiation J. Immunol., January 15, 2005; 174(2): 983 - 991. [Abstract] [Full Text] [PDF]

				I. J. Frew, V. E. Hammond, R. A. Dickins, J. M. W. Quinn, C. R. Walkley, N. A. Sims, R. Schnall, N. G. Della, A. J. Holloway, M. R. Digby, et al. Generation and Analysis of Siah2 Mutant Mice Mol. Cell. Biol., December 15, 2003; 23(24): 9150 - 9161. [Abstract] [Full Text] [PDF]

				P. Shore, W. Dietrich, and L. M. Corcoran Oct-2 regulates CD36 gene expression via a consensus octamer, which excludes the co-activator OBF-1 Nucleic Acids Res., April 15, 2002; 30(8): 1767 - 1773. [Abstract] [Full Text] [PDF]

				R. Grumont, H. Hochrein, M. O'Keeffe, R. Gugasyan, C. White, I. Caminschi, W. Cook, and S. Gerondakis c-Rel Regulates Interleukin 12 p70 Expression in CD8+ Dendritic Cells by Specifically Inducing p35 Gene Transcription J. Exp. Med., October 8, 2001; 194(8): 1021 - 1032. [Abstract] [Full Text] [PDF]

				U. D. Bajpai, K. Zhang, M. Teutsch, R. Sen, and H. H. Wortis Bruton's Tyrosine Kinase Links the B Cell Receptor to Nuclear Factor {kappa}B Activation J. Exp. Med., May 15, 2000; 191(10): 1735 - 1744. [Abstract] [Full Text] [PDF]

				J. Feuillard, S. Memet, B. Goudeau, A. Lilienbaum, R. Schmidt-Ullrich, M. Raphael, and A. Israel In vivo identification of lymphocyte subsets exhibiting transcriptionally active NF-{kappa}B/Rel complexes Int. Immunol., May 1, 2000; 12(5): 613 - 621. [Abstract] [Full Text] [PDF]

				E. R. Fields, B. J. Seufzer, E. M. Oltz, and S. Miyamoto A Switch in Distinct I{kappa}B{alpha} Degradation Mechanisms Mediates Constitutive NF-{kappa}B Activation in Mature B Cells J. Immunol., May 1, 2000; 164(9): 4762 - 4767. [Abstract] [Full Text] [PDF]

				R. J. Grumont and S. Gerondakis Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes: Modulation of Interferon-regulated Gene Expression by Rel/Nuclear Factor {kappa}B J. Exp. Med., April 10, 2000; 191(8): 1281 - 1292. [Abstract] [Full Text] [PDF]

				S. Doerre and R. B. Corley Constitutive Nuclear Translocation of NF-{kappa}B in B Cells in the Absence of I{kappa}B Degradation J. Immunol., July 1, 1999; 163(1): 269 - 277. [Abstract] [Full Text] [PDF]

				A. M. Sheehy and M. S. Schlissel Overexpression of RelA Causes G1 Arrest and Apoptosis in a Pro-B Cell Line J. Biol. Chem., March 26, 1999; 274(13): 8708 - 8716. [Abstract] [Full Text] [PDF]

				R. J. Grumont, I. J. Rourke, and S. Gerondakis Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis Genes & Dev., February 15, 1999; 13(4): 400 - 411. [Abstract] [Full Text]

				S. Miyamoto, B. J. Seufzer, and S. D. Shumway Novel Ikappa Balpha Proteolytic Pathway in WEHI231 Immature B Cells Mol. Cell. Biol., January 1, 1998; 18(1): 19 - 29. [Abstract] [Full Text]

				H. Yasui, W. Butscher, M. Cohen, N. Spriggs, R. Wersto, E. C. Kohn, L. Liotta, and K. Gardner Selective Inhibition of Mitogen-induced Transactivation of the HIV Long Terminal Repeat by Carboxyamidotriazole. CALCIUM INFLUX BLOCKADE REPRESSES HIV-1 TRANSCRIPTIONAL ACTIVATION J. Biol. Chem., November 7, 1997; 272(45): 28762 - 28770. [Abstract] [Full Text] [PDF]

				F Kontgen, R J Grumont, A Strasser, D Metcalf, R Li, D Tarlinton, and S Gerondakis Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes & Dev., August 15, 1995; 9(16): 1965 - 1977. [Abstract] [PDF]