This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Giebler, H. A.
Right arrow Articles by Nyborg, J. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giebler, H. A.
Right arrow Articles by Nyborg, J. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2000, p. 4849-4858, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation

Holli A. Giebler, Isabelle Lemasson, and Jennifer K. Nyborg*

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870

Received 29 December 1999/Returned for modification 16 February 2000/Accepted 23 March 2000

CREB binding protein (CBP) is a 270-kDa nuclear protein required for activated transcription of a large number of cellular genes. Although CBP was originally discovered through its interaction with phosphorylated CREB (pCREB), it is utilized by a multitude of cellular transcription factors and viral oncoproteins. Both CREB and the tumor suppressor p53 have been shown to directly interact with the KIX domain of CBP. Although coactivator competition is an emerging theme in transcriptional regulation, we have made the fortuitous observation that protein kinase A-phosphorylated CREB strongly enhances p53 association with KIX. Phosphorylated CREB also facilitates interaction of a p53 mutant, defective for KIX binding, indicating that CREB functions in a novel way to bridge p53 and the coactivator. This is accomplished through direct interaction between the bZIP domain of CREB and the amino terminus of p53; a protein-protein interaction that is also detected in vivo. Consistent with our biochemical observations, we show that stimulation of the intracellular cyclic AMP (cAMP) pathway, which leads to CREB phosphorylation, strongly enhances both the transcriptional activation and apoptotic properties of p53. We propose that phosphorylated CREB mediates recruitment of CBP to p53-responsive promoters through direct interaction with p53. These observations provide evidence for a novel pathway that integrates cAMP signaling and p53 transcriptional activity.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870. Phone: (970) 491-0420. Fax: (970) 491-0494. E-mail: jnyborg{at}lamar.colostate.edu.

Molecular and Cellular Biology, July 2000, p. 4849-4858, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kelley-Clarke, B., De Leon-Vazquez, E., Slain, K., Barbera, A. J., Kaye, K. M. (2009). Role of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal LANA Chromosome Binding in Episome Persistence. J. Virol. 83: 4326-4337 [Abstract] [Full Text]  
  • Rossi, M., Demidov, O. N., Anderson, C. W., Appella, E., Mazur, S. J. (2008). Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites. Nucleic Acids Res 36: 7168-7180 [Abstract] [Full Text]  
  • Shen, B., Harrison-Bernard, L. M., Fuller, A. J., Vanderpool, V., Saifudeen, Z., El-Dahr, S. S. (2007). The Bradykinin B2 Receptor Gene Is a Target of Angiotensin II Type 1 Receptor Signaling. J. Am. Soc. Nephrol. 18: 1140-1149 [Abstract] [Full Text]  
  • Lemasson, I., Lewis, M. R., Polakowski, N., Hivin, P., Cavanagh, M.-H., Thebault, S., Barbeau, B., Nyborg, J. K., Mesnard, J.-M. (2007). Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Protein Interacts with the Cellular Transcription Factor CREB To Inhibit HTLV-1 Transcription. J. Virol. 81: 1543-1553 [Abstract] [Full Text]  
  • Scian, M. J., Stagliano, K. E. R., Anderson, M. A. E., Hassan, S., Bowman, M., Miles, M. F., Deb, S. P., Deb, S. (2005). Tumor-Derived p53 Mutants Induce NF-{kappa}B2 Gene Expression. Mol. Cell. Biol. 25: 10097-10110 [Abstract] [Full Text]  
  • Saifudeen, Z., Dipp, S., Fan, H., El-Dahr, S. S. (2005). Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation. Am. J. Physiol. Renal Physiol. 288: F899-F909 [Abstract] [Full Text]  
  • Mynard, V., Latchoumanin, O., Guignat, L., Devin-Leclerc, J., Bertagna, X., Barre, B., Fagart, J., Coqueret, O., Catelli, M. G. (2004). Synergistic Signaling by Corticotropin-Releasing Hormone and Leukemia Inhibitory Factor Bridged by Phosphorylated 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein at the Nur Response Element (NurRE)-Signal Transducers and Activators of Transcription (STAT) Element of the Proopiomelanocortin Promoter. Mol. Endocrinol. 18: 2997-3010 [Abstract] [Full Text]  
  • Scian, M. J., Stagliano, K. E. R., Ellis, M. A., Hassan, S., Bowman, M., Miles, M. F., Deb, S. P., Deb, S. (2004). Modulation of Gene Expression by Tumor-Derived p53 Mutants. Cancer Res. 64: 7447-7454 [Abstract] [Full Text]  
  • Wong, L.-Y., Matchett, G. A., Wilson, A. C. (2004). Transcriptional Activation by the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Is Facilitated by an N-Terminal Chromatin-Binding Motif. J. Virol. 78: 10074-10085 [Abstract] [Full Text]  
  • Wang, Z., Zhang, B., Wang, M., Carr, B. I. (2003). Persistent ERK Phosphorylation Negatively Regulates cAMP Response Element-binding Protein (CREB) Activity via Recruitment of CREB-binding Protein to pp90RSK. J. Biol. Chem. 278: 11138-11144 [Abstract] [Full Text]  
  • Goto, N. K., Zor, T., Martinez-Yamout, M., Dyson, H. J., Wright, P. E. (2002). Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP). THE MIXED LINEAGE LEUKEMIA PROTEIN (MLL) ACTIVATION DOMAIN BINDS TO AN ALLOSTERIC SITE ON THE KIX DOMAIN. J. Biol. Chem. 277: 43168-43174 [Abstract] [Full Text]  
  • Zor, T., Mayr, B. M., Dyson, H. J., Montminy, M. R., Wright, P. E. (2002). Roles of Phosphorylation and Helix Propensity in the Binding of the KIX Domain of CREB-binding Protein by Constitutive (c-Myb) and Inducible (CREB) Activators. J. Biol. Chem. 277: 42241-42248 [Abstract] [Full Text]  
  • Wang, Z., Wang, M., Lazo, J. S., Carr, B. I. (2002). Identification of Epidermal Growth Factor Receptor as a Target of Cdc25A Protein Phosphatase. J. Biol. Chem. 277: 19470-19475 [Abstract] [Full Text]  
  • Ogawa, R., Streiff, M. B., Bugayenko, A., Kato, G. J. (2002). Inhibition of PDE4 phosphodiesterase activity induces growth suppression, apoptosis, glucocorticoid sensitivity, p53, and p21WAF1/CIP1 proteins in human acute lymphoblastic leukemia cells. Blood 99: 3390-3397 [Abstract] [Full Text]  
  • Leicht, M., Briest, W., Holzl, A., Zimmer, H.-G. (2001). Serum depletion induces cell loss of rat cardiac fibroblasts and increased expression of extracellular matrix proteins in surviving cells. Cardiovasc Res 52: 429-437 [Abstract] [Full Text]  
  • Jaitovich-Groisman, I., Benlimame, N., Slagle, B. L., Perez, M. H., Alpert, L., Song, D. J., Fotouhi-Ardakani, N., Galipeau, J., Alaoui-Jamali, M. A. (2001). Transcriptional Regulation of the TFIIH Transcription Repair Components XPB and XPD by the Hepatitis B Virus x Protein in Liver Cells and Transgenic Liver Tissue. J. Biol. Chem. 276: 14124-14132 [Abstract] [Full Text]  
  • Lemasson, I., Nyborg, J. K. (2001). Human T-cell Leukemia Virus Type I Tax Repression of p73beta Is Mediated through Competition for the C/H1 Domain of CBP. J. Biol. Chem. 276: 15720-15727 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»