Structural and Functional Analysis of NF-κB: Determinants of DNA Binding Specificity and Protein Interaction

Roland M. Schmid, Susanne Liptay, Jonathan C. Betts, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

The NF-κB transcription factors display a high degree of sequence conservation in a domain initially described in the rel oncogene. Two family members, NF-κB1 and NF-κB2, have distinct DNA binding properties and functionally distinct effects on different enhancers. NF-κB1, for example, binds to the κB site from the human immunodeficiency virus (HIV) with ∼15-fold higher affinity than NF-κB2. In this study, we have defined regions within the Rel domain which determine DNA binding specificity and interaction with other proteins. We find that the COOH-terminal putative Rel dimerization domain of NF-κB1 is required for preferential binding to the HIV κB site. In contrast, preferential stimulation of the HIV enhancer by NF-κB2 with RelA(p65) is determined by both the NH2- and COOH-terminal Rel domains of NF-κB2. These two regions of NF-κB2 also mediate preferential synergy with Bc13. These data suggest that a specific subdomain of the Rel conserved region has evolved to control the fine specificity of DNA binding, and two distinct subrogions within the Rel domain determine the specificity of interaction with other transcription factors. These specific Rel-conserved domains therefore determine the specificity of NF-κB interactions and contribute to selective gene activation.

Original languageEnglish (US)
Pages (from-to)32162-32167
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number51
StatePublished - Dec 23 1994
Externally publishedYes

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Functional analysis
DNA-Binding Proteins
Viruses
Structural analysis
HIV
rel Genes
DNA
Transcription Factors
Proteins
Dimerization
Transcriptional Activation
Conservation
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structural and Functional Analysis of NF-κB : Determinants of DNA Binding Specificity and Protein Interaction. / Schmid, Roland M.; Liptay, Susanne; Betts, Jonathan C.; Nabel, Gary J.

In: Journal of Biological Chemistry, Vol. 269, No. 51, 23.12.1994, p. 32162-32167.

Research output: Contribution to journalArticle

Schmid, Roland M. ; Liptay, Susanne ; Betts, Jonathan C. ; Nabel, Gary J. / Structural and Functional Analysis of NF-κB : Determinants of DNA Binding Specificity and Protein Interaction. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 51. pp. 32162-32167.
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