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Science 24 January 1997:
Vol. 275. no. 5299, pp. 523 - 527
DOI: 10.1126/science.275.5299.523
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Reports

Regulation of NF-kappa B 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 dagger

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

N. D. Perkins, L. K. Felzien, J. C. Betts, K. Leung, G. J. Nabel, Howard Hughes Medical Institute, Departments of Internal Medicine and Biological Chemistry, University of Michigan Medical Center, 4520 MSRB I, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
D. H. Beach, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Bungtown Road, Cold Spring Harbor, NY 11724, USA.
*   Present address: Department of Biochemistry, Medical Sciences Institute, University of Dundee, Dundee DD1 4HN, Scotland, UK.

dagger    To whom correspondence should be addressed.

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   Abstract »    Full Text »    PDF »
NF-{kappa}B1 Is Required for Optimal CD4+ Th1 Cell Development and Resistance to Leishmania major.
D. Artis, K. Speirs, K. Joyce, M. Goldschmidt, J. Caamano, C. A. Hunter, and P. Scott (2003)
J. Immunol. 170, 1995-2003
   Abstract »    Full Text »    PDF »
Inhibition of I{kappa}B Kinase by a New Class of Retinoid-Related Anticancer Agents That Induce Apoptosis.
Y. Bayon, M. A. Ortiz, F. J. Lopez-Hernandez, F. Gao, M. Karin, M. Pfahl, and F. J. Piedrafita (2003)
Mol. Cell. Biol. 23, 1061-1074
   Abstract »    Full Text »
Flavopiridol-related Proinflammatory Syndrome Is Associated with Induction of Interleukin-6.
R. A. Messmann, C. D. Ullmann, T. Lahusen, A. Kalehua, J. Wasfy, G. Melillo, I. Ding, D. Headlee, W. D. Figg, E. A. Sausville, et al. (2003)
Clin. Cancer Res. 9, 562-570
   Abstract »    Full Text »    PDF »
Post-activation Turn-off of NF-kappa B-dependent Transcription Is Regulated by Acetylation of p65.
R. Kiernan, V. Bres, R. W. M. Ng, M.-P. Coudart, S. El Messaoudi, C. Sardet, D.-Y. Jin, S. Emiliani, and M. Benkirane (2003)
J. Biol. Chem. 278, 2758-2766
   Abstract »    Full Text »    PDF »
Regulation of RelA (p65) Function by the Large Subunit of Replication Factor C.
L. A. Anderson and N. D. Perkins (2003)
Mol. Cell. Biol. 23, 721-732
   Abstract »    Full Text »    PDF »
The Transcriptional Coactivator CREB-binding Protein Cooperates with STAT1 and NF-kappa B for Synergistic Transcriptional Activation of the CXC Ligand 9/Monokine Induced by Interferon-gamma Gene.
M. Hiroi and Y. Ohmori (2003)
J. Biol. Chem. 278, 651-660
   Abstract »    Full Text »    PDF »
Identification of a Nuclear Factor Kappa B-dependent Gene Network.
B. Tian and A. R. Brasier (2003)
Recent Prog. Horm. Res. 58, 95-130
   Abstract »    Full Text »    PDF »
Oct-1 Potentiates CREB-Driven Cyclin D1 Promoter Activation via a Phospho-CREB- and CREB Binding Protein-Independent Mechanism.
S. Boulon, J.-C. Dantonel, V. Binet, A. Vie, J.-M. Blanchard, R. A. Hipskind, and A. Philips (2002)
Mol. Cell. Biol. 22, 7769-7779
   Abstract »    Full Text »    PDF »
Stimulation of DNA Replication from the Polyomavirus Origin by PCAF and GCN5 Acetyltransferases: Acetylation of Large T Antigen.
A.-Y. Xie, V. P. Bermudez, and W. R. Folk (2002)
Mol. Cell. Biol. 22, 7907-7918
   Abstract »    Full Text »    PDF »
IKKalpha , IKKbeta , and NEMO/IKKgamma Are Each Required for the NF-kappa B-mediated Inflammatory Response Program.
X. Li, P. E. Massa, A. Hanidu, G. W. Peet, P. Aro, A. Savitt, S. Mische, J. Li, and K. B. Marcu (2002)
J. Biol. Chem. 277, 45129-45140
   Abstract »    Full Text »    PDF »
Novel Function of the Transactivation Domain of a Pituitary-specific Transcription Factor, Pit-1.
M. Kishimoto, Y. Okimura, K. Yagita, G. Iguchi, M. Fumoto, K. Iida, H. Kaji, H. Okamura, and K. Chihara (2002)
J. Biol. Chem. 277, 45141-45148
   Abstract »    Full Text »    PDF »
P21WAF1 CONTROL OF EPITHELIAL CELL CYCLE AND CELL FATE.
W. C. Weinberg and M. F. Denning (2002)
Critical Reviews in Oral Biology & Medicine 13, 453-464
   Abstract »    Full Text »    PDF »
Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-{kappa}B and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies.
V. Quivy, E. Adam, Y. Collette, D. Demonte, A. Chariot, C. Vanhulle, B. Berkhout, R. Castellano, Y. de Launoit, A. Burny, et al. (2002)
J. Virol. 76, 11091-11103
   Abstract »    Full Text »    PDF »
NRC-Interacting Factor 1 Is a Novel Cotransducer That Interacts with and Regulates the Activity of the Nuclear Hormone Receptor Coactivator NRC.
M. A. Mahajan, A. Murray, and H. H. Samuels (2002)
Mol. Cell. Biol. 22, 6883-6894
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Physical and Functional Interaction of HIV-1 Tat with E2F-4, a Transcriptional Regulator of Mammalian Cell Cycle.
C. Ambrosino, C. Palmieri, A. Puca, F. Trimboli, M. Schiavone, F. Olimpico, M. R. Ruocco, F. di Leva, M. Toriello, I. Quinto, et al. (2002)
J. Biol. Chem. 277, 31448-31458
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Down Regulation of the Interleukin-8 Promoter by Human Papillomavirus Type 16 E6 and E7 through Effects on CREB Binding Protein/p300 and P/CAF.
S.-M. Huang and D. J. McCance (2002)
J. Virol. 76, 8710-8721
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Role of the E1A Rb-binding domain in repression of the NF-kappa B-dependent defense against tumor necrosis factor-alpha.
J. L. Cook, T. A. Walker, G. S. Worthen, and J. R. Radke (2002)
PNAS 99, 9966-9971
   Abstract »    Full Text »    PDF »
Increased p300 Expression Inhibits Glucocorticoid Receptor-T-Cell Receptor Antagonism but Does Not Affect Thymocyte Positive Selection.
C.-T. Yu, M.-H. L. Feng, H.-m. Shih, and M.-Z. Lai (2002)
Mol. Cell. Biol. 22, 4556-4566
   Abstract »    Full Text »    PDF »


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