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

A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator.

Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, United Kingdom.

ABSTRACT

The mammalian transcriptional activator CREB binds as a dimer to a broad spectrum of inducible promoters. CREB activity is modulated by several signalling agents (protein kinase A [PKA], Ca2+, and transforming growth factor beta) and via functional interactions with cell-specific transcription factors. In addition, CREB can activate transcription constitutively and repress the activity of several other transcriptional activators. The mechanisms that allow CREB to act in such a malleable manner and the role that CREB dimerization might play in this are poorly understood. To probe the latter issue, we have created monomeric forms of CREB by fusing CREB to the DNA-binding domain of a protein (B-cell specific activator protein [BSAP]) that binds to DNA as a monomer. Remarkably, monomeric CREB acts as a potent, constitutive activator under conditions in which native CREB is inducible by PKA. Thus, CREB contains constitutive activation regions that are unable to function in native CREB. Two glutamine-rich domains that are important for native, PKA-inducible CREB activity are required for the constitutive activity of monomeric CREB. In contrast, two elements within the kinase-inducible domain of CREB are dispensable for constitutive activity. We discuss our results in relation to inducible and constitutive CREB activity and the potential modes of action of other activators that directly interact with CREB.

This article has been cited by other articles:

• Alex, D., Lee, K. A. W. (2005). RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation domains. Nucleic Acids Res 33: 1323-1331 [Abstract] [Full Text]  
• Krajewski, W. A., Nakamura, T., Mazo, A., Canaani, E. (2005). A Motif within SET-Domain Proteins Binds Single-Stranded Nucleic Acids and Transcribed and Supercoiled DNAs and Can Interfere with Assembly of Nucleosomes. Mol. Cell. Biol. 25: 1891-1899 [Abstract] [Full Text]  
• Wu, X., Spiro, C., Owen, W. G., McMurray, C. T. (1998). cAMP Response Element-binding Protein Monomers Cooperatively Assemble to Form Dimers on DNA. J. Biol. Chem. 273: 20820-20827 [Abstract] [Full Text]  
• Wu, X., McMurray, C. T. (2001). Calmodulin Kinase II Attenuation of Gene Transcription by Preventing cAMP Response Element-binding Protein (CREB) Dimerization and Binding of the CREB-binding Protein. J. Biol. Chem. 276: 1735-1741 [Abstract] [Full Text]