This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duckett, C S Articles by Nabel, G J Search for Related Content PubMed PubMed Citation Articles by Duckett, C S Articles by Nabel, G J

Next Article 

Mol Cell Biol. 1993 March; 13(3): 1315-1322

Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3).

Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650.

ABSTRACT

Inducible expression of human immunodeficiency virus (HIV) is regulated by a cellular transcription factor, nuclear factor kappa B (NF-kappa B). NF-kappa B is composed of distinct subunits; five independent genes, NFKB1(p105), NFKB2(p100), RelA(p65), c-rel and relB, that encode related proteins that bind to kappa B DNA elements have been isolated. We have previously found that NFKB2(p49/p52) acts in concert with RelA(p65) to stimulate the HIV enhancer in Jurkat T-leukemia cells. Here we examine the biochemical basis for the transcriptional regulation of HIV by NFKB2. Using Scatchard analysis, we have determined the dissociation constants of homodimeric p49 and heterodimeric p49/p65 for binding to the HIV kappa B site. p49 has a approximately 18-fold-lower affinity for the HIV kappa B site (KD = 69.1 pM) than does the approximately 50-kDa protein NFKB1(p50) derived from p105 (KD = 3.9 pM). In contrast, the affinity of heterodimeric NFKB2(p49)/RelA(p65) for this site is approximately 6-fold higher (KD = 11.8 pM) than that of p49 alone. Consistent with these findings, in vitro transcription was stimulated 18-fold by the addition of preformed, heterodimeric NFKB2(p49)/RelA(p65) protein. Transcriptional activation of the HIV enhancer was also subject to regulation by recently cloned I kappa B-alpha(MAD-3). Recombinant I kappa B-alpha(MAD-3) inhibited the DNA binding activity of p65, p49/p65, and p50/p65 but stimulated the binding of NFKB2(p49) or NFKB1(p50). Functional activation of an HIV reporter plasmid by p49/p65 in transiently transfected Jurkat T-leukemia cells was also inhibited by coexpression of MAD-3. These data suggest that binding of the NFKB2 subunit to the HIV enhancer is facilitated by RelA(p65) and that this NFKB2(p49)/p65 heterodimeric complex mediates transcriptional activation which is subject to regulation by MAD-3.

This article has been cited by other articles:

• Battaglia, F., Delfino, S., Merello, E., Puppo, M., Piva, R., Varesio, L., Bosco, M. C. (2008). Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B. J. Leukoc. Biol. 83: 648-662 [Abstract] [Full Text]  
• Cheng, J., Kydd, A. R., Nakase, K., Noonan, K. M., Murakami, A., Tao, H., Dwyer, M., Xu, C., Zhu, Q., Marasco, W. A. (2007). Negative regulation of the SH2-homology containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein. Blood 110: 2110-2120 [Abstract] [Full Text]  
• Ganesh, L., Yoshimoto, T., Moorthy, N. C., Akahata, W., Boehm, M., Nabel, E. G., Nabel, G. J. (2006). Protein Methyltransferase 2 Inhibits NF-{kappa}B Function and Promotes Apoptosis. Mol. Cell. Biol. 26: 3864-3874 [Abstract] [Full Text]  
• Burstein, E., Hoberg, J. E., Wilkinson, A. S., Rumble, J. M., Csomos, R. A., Komarck, C. M., Maine, G. N., Wilkinson, J. C., Mayo, M. W., Duckett, C. S. (2005). COMMD Proteins, a Novel Family of Structural and Functional Homologs of MURR1. J. Biol. Chem. 280: 22222-22232 [Abstract] [Full Text]  
• Serio, K. J., Reddy, K. V., Bigby, T. D. (2005). Lipopolysaccharide induces 5-lipoxygenase-activating protein gene expression in THP-1 cells via a NF-{kappa}B and C/EBP-mediated mechanism. Am. J. Physiol. Cell Physiol. 288: C1125-C1133 [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]  
• Demarchi, F., Bertoli, C., Sandy, P., Schneider, C. (2003). Glycogen Synthase Kinase-3{beta} Regulates NF-{kappa}B1/p105 Stability. J. Biol. Chem. 278: 39583-39590 [Abstract] [Full Text]  
• Novack, D. V., Yin, L., Hagen-Stapleton, A., Schreiber, R. D., Goeddel, D. V., Ross, F. P., Teitelbaum, S. L. (2003). The I{kappa}B Function of NF-{kappa}B2 p100 Controls Stimulated Osteoclastogenesis. J. Exp. Med. 198: 771-781 [Abstract] [Full Text]  
• Adam, E., Quivy, V., Bex, F., Chariot, A., Collette, Y., Vanhulle, C., Schoonbroodt, S., Goffin, V., Nguyen, T. L.-A., Gloire, G., Carrard, G., Friguet, B., de Launoit, Y., Burny, A., Bours, V., Piette, J., Van Lint, C. (2003). Potentiation of Tumor Necrosis Factor-Induced NF-{kappa}B Activation by Deacetylase Inhibitors Is Associated with a Delayed Cytoplasmic Reappearance of I{kappa}B{alpha}. Mol. Cell. Biol. 23: 6200-6209 [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]  
• Serio, K. J., Johns, S. C., Luo, L., Hodulik, C. R., Bigby, T. D. (2003). Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1. J. Immunol. 170: 2121-2128 [Abstract] [Full Text]  
• West, M. J., Lowe, A. D., Karn, J. (2001). Activation of Human Immunodeficiency Virus Transcription in T Cells Revisited: NF-{kappa}B p65 Stimulates Transcriptional Elongation. J. Virol. 75: 8524-8537 [Abstract] [Full Text]  
• Mir, S. S., Richter, B. W. M., Duckett, C. S. (2000). Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells. Blood 96: 4307-4312 [Abstract] [Full Text]  
• Menetski, J. P. (2000). The Structure of the Nuclear Factor-kappa B Protein-DNA Complex Varies with DNA-binding Site Sequence. J. Biol. Chem. 275: 7619-7625 [Abstract] [Full Text]  
• Murakami, S., Lefebvre, V., de Crombrugghe, B. (2000). Potent Inhibition of the Master Chondrogenic Factor Sox9 Gene by Interleukin-1 and Tumor Necrosis Factor-alpha. J. Biol. Chem. 275: 3687-3692 [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]  
• Han, B., Logsdon, C. D. (1999). Cholecystokinin induction of mob-1 chemokine expression in pancreatic acinar cells requires NF-kappa B activation. Am. J. Physiol. Cell Physiol. 277: C74-C82 [Abstract] [Full Text]  
• Kouba, D. J., Chung, K.-Y., Nishiyama, T., Vindevoghel, L., Kon, A., Klement, J. F., Uitto, J., Mauviel, A. (1999). Nuclear Factor-{kappa}B Mediates TNF-{alpha} Inhibitory Effect on {alpha}2(I) Collagen (COL1A2) Gene Transcription in Human Dermal Fibroblasts. J. Immunol. 162: 4226-4234 [Abstract] [Full Text]  
• Guermah, M., Malik, S., Roeder, R. G. (1998). Involvement of TFIID and USA Components in Transcriptional Activation of the Human Immunodeficiency Virus Promoter by NF-kappa B and Sp1. Mol. Cell. Biol. 18: 3234-3244 [Abstract] [Full Text]  
• Johnson, R. J., Stack, M., Hazlewood, S. A., Jones, M., Blackmore, C. G., Hu, L.-F., Rowe, M. (1998). The 30-Base-Pair Deletion in Chinese Variants of the Epstein-Barr Virus LMP1 Gene Is Not the Major Effector of Functional Differences between Variant LMP1 Genes in Human Lymphocytes. J. Virol. 72: 4038-4048 [Abstract] [Full Text]  
• Felzien, L. K., Woffendin, C., Hottiger, M. O., Subbramanian, R. A., Cohen, E. A., Nabel, G. J. (1998). HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc. Natl. Acad. Sci. USA 95: 5281-5286 [Abstract] [Full Text]  
• Oswald, F., Liptay, S., Adler, G., Schmid, R. M. (1998). NF-kappa B2 Is a Putative Target Gene of Activated Notch-1 via RBP-Jkappa. Mol. Cell. Biol. 18: 2077-2088 [Abstract] [Full Text]  
• Bundy, D. L., McKeithan, T. W. (1997). Diverse Effects of BCL3 Phosphorylation on Its Modulation of NF-kappa B p52 Homodimer Binding to DNA. J. Biol. Chem. 272: 33132-33139 [Abstract] [Full Text]  
• Sica, A., Dorman, L., Viggiano, V., Cippitelli, M., Ghosh, P., Rice, N., Young, H. A. (1997). Interaction of NF-kappa B and NFAT with the Interferon-gamma Promoter. J. Biol. Chem. 272: 30412-30420 [Abstract] [Full Text]  
• Ishikawa, H., Carrasco, D., Claudio, E., Ryseck, R.-P., Bravo, R. (1997). Gastric Hyperplasia and Increased Proliferative Responses of Lymphocytes in Mice Lacking the COOH-terminal Ankyrin Domain of NF-kappa B2. J. Exp. Med. 186: 999-1014 [Abstract] [Full Text]  
• Basile, A., Sica, A., d'Aniello, E., Breviario, F., Garrido, G., Castellano, M., Mantovani, A., Introna, M. (1997). Characterization of the Promoter for the Human Long Pentraxin PTX3. ROLE OF NF-kappa B IN TUMOR NECROSIS FACTOR-alpha AND INTERLEUKIN-1beta REGULATION. J. Biol. Chem. 272: 8172-8178 [Abstract] [Full Text]  
• Foreman, K. E., Friborg, J., Kong, W.-p., Woffendin, C., Polverini, P. J., Nickoloff, B. J., Nabel, G. J. (1997). Propagation of a Human Herpesvirus from AIDS-Associated Kaposi's Sarcoma. NEJM 336: 163-171 [Abstract] [Full Text]  
• Pazin, M J, Sheridan, P L, Cannon, K, Cao, Z, Keck, J G, Kadonaga, J T, Jones, K A (1996). NF-kappa B-mediated chromatin reconfiguration and transcriptional activation of the HIV-1 enhancer in vitro.. Genes Dev. 10: 37-49 [Abstract]  
• Duckett, C. S., Perkins, N. D., Leung, K., Agranoff, A. B., Nabel, G. J. (1995). Cytokine Induction of Nuclear Factor kappaB in Cycling and Growth-arrested Cells. J. Biol. Chem. 270: 18836-18840 [Abstract] [Full Text]  
• Lin, R., Gewert, D., Hiscott, J. (1995). Differential Transcriptional Activation in Vitro by NF-kappaB/Rel Proteins. J. Biol. Chem. 270: 3123-3131 [Abstract] [Full Text]  
• Phelps, C. B., Sengchanthalangsy, L. L., Malek, S., Ghosh, G. (2000). Mechanism of kappa B DNA binding by Rel/NF-kappa B dimers. J. Biol. Chem. 275: 24392-24399 [Abstract] [Full Text]  
• Denk, A., Goebeler, M., Schmid, S., Berberich, I., Ritz, O., Lindemann, D., Ludwig, S., Wirth, T. (2001). Activation of NF-kappa B via the Ikappa B Kinase Complex Is Both Essential and Sufficient for Proinflammatory Gene Expression in Primary Endothelial Cells. J. Biol. Chem. 276: 28451-28458 [Abstract] [Full Text]