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- Title
Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator.
- Authors
Perkins, N D; Felzien, L K; Betts, J C; Leung, K; Beach, D H; Nabel, G J
- 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
Science (New York, N.Y.), 1997, Vol 275, Issue 5299, p523
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.275.5299.523