Abstract
The nuclear factor kappaB (NF-kappaB) transcription factor is responsive to specific cytokines and stress and is often activated in association with cell damage and growth arrest in eukaryotes. NF-kappaB is a heterodimeric protein, typically composed of 50- and 65-kilodalton subunits of the Rel family, of which RelA(p65) stimulates transcription of diverse genes. Specific cyclin-dependent kinases (CDKs) were found to regulate transcriptional activation by NF-kappaB through interactions with the coactivator p300. The transcriptional activation domain of RelA(p65) interacted with an amino-terminal region of p300 distinct from a carboxyl-terminal region of p300 required for binding to the cyclin E-Cdk2 complex. The CDK inhibitor p21 or a dominant negative Cdk2, which inhibited p300-associated cyclin E-Cdk2 activity, stimulated kappaB-dependent gene expression, which was also enhanced by expression of p300 in the presence of p21. The interaction of NF-kappaB and CDKs through the p300 and CBP coactivators provides a mechanism for the coordination of transcriptional activation with cell cycle progression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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CDC2-CDC28 Kinases*
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Cell Cycle
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Cell Line
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism*
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Cyclins / genetics
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Cyclins / metabolism
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Genes, Reporter
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Humans
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Jurkat Cells
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Signal Transduction
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Tetradecanoylphorbol Acetate / pharmacology
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Trans-Activators*
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Transcription Factor RelA
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Transfection
Substances
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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NF-kappa B
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Nuclear Proteins
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Trans-Activators
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Transcription Factor RelA
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Transcription Factors
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Protein Kinases
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histone H1 kinase
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases
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Tetradecanoylphorbol Acetate