Regulation of NF-κB by cyclin-dependent kinases associated with the p300 coactivator

Neil D. Perkins, Lisa K. Felzien, Jonathan C. Betts, Kwanyee Leung, David H. Beach, Gary J. Nabel

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Abstract

The nuclear factor κB (NF-κB) transcription factor is responsive to specific cytokines and stress and is often activated in association with cell damage and growth arrest in eukaryotes. NF-κB 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-κB 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 κB- dependent gene expression, which was also enhanced by expression of p300 in the presence of p21. The interaction of NF-κB and CDKs through the p300 and CBP coactivators provides a mechanism for the coordination of transcriptional activation with cell cycle progression.

Original languageEnglish (US)
Pages (from-to)523-527
Number of pages5
JournalScience
Volume275
Issue number5299
DOIs
StatePublished - Jan 24 1997
Externally publishedYes

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Cite this

Perkins, N. D., Felzien, L. K., Betts, J. C., Leung, K., Beach, D. H., & Nabel, G. J. (1997). Regulation of NF-κB by cyclin-dependent kinases associated with the p300 coactivator. Science, 275(5299), 523-527. https://doi.org/10.1126/science.275.5299.523