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 Bressler, P Articles by Fauci, A S Search for Related Content PubMed PubMed Citation Articles by Bressler, P Articles by Fauci, A S

Mutational analysis of the p50 subunit of NF-kappa B and inhibition of NF-kappa B activity by trans-dominant p50 mutants.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

ABSTRACT

The NF-kappa B family of DNA-binding proteins regulates the expression of many cellular and viral genes. Each of these proteins has an N-terminal region that is homologous to the c-Rel proto-oncogene product, and this Rel homology region defines both DNA binding and protein dimerization properties of the individual proteins. Most of the NF-kappa B family members have been shown to associate with themselves or with each other to form homodimers or heterodimers, and previous studies have shown that dimerization of NF-kappa B factors is necessary to provide a functional DNA binding domain. We have used site-directed mutagenesis to identify regions in the Rel homology domain of the p50/NF-kappa B protein that are important for DNA binding and protein dimerization. Our studies have identified mutations of p50 that interfere with DNA binding only and those that interfere with protein dimerization. Mutations of p50 which disrupt only DNA binding were still able to associate with other members of the NF-kappa B protein family. We demonstrate that such heterodimeric complexes inhibit transcriptional activation mediated in trans through a cis-acting kappa B motif; therefore, we have identified trans-dominant negative mutants of p50.

This article has been cited by other articles:

• Liss, A. S., Bose, H. R. Jr. (2002). Mutational Analysis of the v-Rel Dimerization Interface Reveals a Critical Role for v-Rel Homodimers in Transformation. J. Virol. 76: 4928-4939 [Abstract] [Full Text]  
• Nicot, C., Mahieux, R., Pise-Masison, C., Brady, J., Gessain, A., Yamaoka, S., Franchini, G. (2001). Human T-Cell Lymphotropic Virus Type 1 Tax Represses c-Myb-Dependent Transcription through Activation of the NF-{kappa}B Pathway and Modulation of Coactivator Usage. Mol. Cell. Biol. 21: 7391-7402 [Abstract] [Full Text]  
• Ruocco, M. R., Chen, X., Ambrosino, C., Dragonetti, E., Liu, W., Mallardo, M., De Falco, G., Palmieri, C., Franzoso, G., Quinto, I., Venuta, S., Scala, G. (1996). Regulation of HIV-1 Long Terminal Repeats by Interaction of C/EBP(NF-IL6) and NF-kappa B/Rel Transcription Factors. J. Biol. Chem. 271: 22479-22486 [Abstract] [Full Text]  
• Trofimova, M., Sprenkle, A. B., Green, M., Sturgill, T. W., Goebl, M. G., Harrington, M. A. (1996). Developmental and Tissue-specific Expression of Mouse Pelle-like Protein Kinase. J. Biol. Chem. 271: 17609-17612 [Abstract] [Full Text]  
• Baldi, L., Brown, K., Franzoso, G., Siebenlist, U. (1996). Critical Role for Lysines 21 and 22 in Signal-induced, Ubiquitin-mediated Proteolysis of IkappaB-alpha. J. Biol. Chem. 271: 376-379 [Abstract] [Full Text]  
• Muroi, M., Muroi, Y., Ito, N., Rice, N.R., Suzuki, T. (1995). Effects of protease inhibitors on LPS-mediated activation of a mouse macrophage cell line (J774). Innate Immunity 2: 337-347 [Abstract]  
• Brown, K, Gerstberger, S, Carlson, L, Franzoso, G, Siebenlist, U (1995). Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. Science 267: 1485-1488 [Abstract]  
• Jain, J., Burgeon, E., Badalian, T. M., Hogan, P. G., Rao, A. (1995). A Similar DNA-binding Motif in NFAT Family Proteins and the Rel Homology Region. J. Biol. Chem. 270: 4138-4145 [Abstract] [Full Text]