The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1.
Homodimers of the NF-kappa B p50 subunit are transcriptionally repressive in cells, whereas they can promote transcription in vitro, suggesting that their endogenous effects are mediated by association with other factors. We now demonstrate that transcriptionally inactive nuclear NF-kappaB in resting cells consists of homodimers of either p65 or p50 complexed with the histone deacetylase HDAC-1. Only the p50-HDAC-1 complexes bind to DNA and suppress NF-kappa B-dependent gene expression in unstimulated cells. Appropriate stimulation causes nuclear localization of NF-kappa B complexes containing phosphorylated p65 that associates with CBP and displaces the p50-HDAC-1 complexes. Our results demonstrate that phosphorylation of p65 determines whether it associates with either CBP or HDAC-1, ensuring that only p65 entering the nucleus from cytoplasmic NF-kappa B:Ikappa B complexes can activate transcription.
Zhong
Haihong
H
Immunobiology Section and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
May
Michael J
MJ
Jimi
Eijiro
E
Ghosh
Sankar
S
D000123:Acetyltransferases / Q000378:metabolism; D000251:Adenosine Triphosphatases; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases; D019281:Dimerization; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic
D016207:Cytokines; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D004247:DNA; D000123:Acetyltransferases; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D051548:Histone Acetyltransferases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C410222:DNA2 protein, S cerevisiae