Distinct combinations of NF-κB subunits determine the specificity of transcriptional activation

Neil D. Perkins, Roland M. Schmid, Colin S. Duckett, Kwanyee Leung, Nancy R. Rice, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

The nuclear factor that binds to the κ light-chain enhancer of B cells (NF-κB) is a transcription factor that regulates the expression of a variety of cellular and viral genes. NF-κB is composed of distinct subunits, and at least four independent genes (p105, p100, p65, and c-rel) have been isolated that encode related proteins that bind κB sites. Because it is possible that specific interactions of different subunits can allow selective gene activation, we have characterized the specificity of transcriptional activation by various combinations of these subunits. When tested alone, an ≈49-kDa form (p49) of the p100 protein bound weakly to KB, but p49 associated with p65 to bind efficiently to this site. Furthermore, p49 acted in combination with either p65 or a Rel/VP16 fusion protein to activate κB-dependent transcription in Jurkat T leukemia cells. The p49/p65 or p49/Rel combination stimulated transcription mediated by the canonical κB site but did not stimulate reporter genes containing interleukin 2 receptor α or major histocompatibility complex κB elements, despite its ability to bind to these sites. Transactivation mediated by the p49/p100 and p65 NF-κB proteins is therefore sensitive to minor changes in the sequence of the κB site. Specificity determined by the association of NF-κB subunits provides a mechanism to selectively regulate variant κB sites associated with different cellular and viral genes.

Original languageEnglish (US)
Pages (from-to)1529-1533
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number5
StatePublished - 1992
Externally publishedYes

Keywords

  • c-rel gene
  • DNA binding
  • Transactivation

ASJC Scopus subject areas

  • Genetics
  • General

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