Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B.
Recombinant subunits of the transcription factor NF-kappa B, p50 and p65, were analyzed both for binding to various kappa B motifs and in vitro activation. The subunits preferentially form a heterodimer that activates transcription. Although p50 and p65 bind DNA individually as homodimers and are structurally related, their activation mechanisms are distinct. p65 activates transcription by its unique carboxy-terminal activation domain. (p50)2 displays higher affinity DNA binding than (p65)2 for many distinct kappa B motifs and provides strong transcriptional activation only when adopting a chymotrypsin-resistant conformation induced by certain kappa B motifs but not others. Thus, (p50)2 acts as a positive regulator in vitro, consistent with its isolation as a putative constitutive regulator of MHC class I genes. Both subunits of NF-kappa B, therefore, contribute independently to provide regulation at given kappa B motifs.
Fujita
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Nolan
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Ghosh
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Baltimore
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D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases