This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01062-06v1 26/22/8599    most recent 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 Xiang, H. Articles by Boxer, L. M. Search for Related Content PubMed PubMed Citation Articles by Xiang, H. Articles by Boxer, L. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2006, p. 8599-8606, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01062-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of the Cyclic AMP Response Element in the bcl-2 Promoter in the Regulation of Endogenous Bcl-2 Expression and Apoptosis in Murine B Cells

Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System, and Department of Medicine, Stanford University School of Medicine, Stanford, California 94305

Received 13 June 2006/ Returned for modification 16 July 2006/ Accepted 5 September 2006

We have previously shown for B-cell lines that the cyclic AMP response element (CRE) is a major positive regulatory site in the bcl-2 promoter. However, the role of the CRE in the regulation of endogenous bcl-2 expression in vivo has not been characterized. We used gene targeting to generate knock-in mice in which a mutated CRE was introduced into the bcl-2 promoter region (mutCRE-bcl2 mice). Quantitative chromatin immunoprecipitation assays revealed that mutation of the CRE abolished the binding of CREB/ATF and CBP transcription factors to the bcl-2 promoter and greatly diminished the binding of NF-B factors. The mutant CRE significantly reduced the expression of Bcl-2 in B cells and rendered them susceptible to surface immunoglobulin- and chemotherapeutic agent-induced apoptosis. The low levels of Bcl-2 were not changed with activation of the cells. The numbers of pre-B, immature B, and mature B cells in the bone marrow were decreased, as were the numbers of splenic B cells in mutCRE-bcl2 mice. Our findings indicate that the CRE in the bcl-2 promoter has an important functional role in the regulation of endogenous Bcl-2 expression and plays a critical role in the coordination of signals that regulate B-cell survival.

Published ahead of print on 18 September 2006.

This article has been cited by other articles:

• Seo, H.-S., Liu, D. D., Bekele, B. N., Kim, M.-K., Pisters, K., Lippman, S. M., Wistuba, I. I., Koo, J. S. (2008). Cyclic AMP Response Element-Binding Protein Overexpression: A Feature Associated with Negative Prognosis in Never Smokers with Non-Small Cell Lung Cancer. Cancer Res. 68: 6065-6073 [Abstract] [Full Text]  
• Kim, S.-J., Nian, C., Widenmaier, S., McIntosh, C. H. S. (2008). Glucose-Dependent Insulinotropic Polypeptide-Mediated Up-Regulation of {beta}-Cell Antiapoptotic Bcl-2 Gene Expression Is Coordinated by Cyclic AMP (cAMP) Response Element Binding Protein (CREB) and cAMP-Responsive CREB Coactivator 2. Mol. Cell. Biol. 28: 1644-1656 [Abstract] [Full Text]  
• Aggarwal, S., Kim, S.-W., Ryu, S.-H., Chung, W.-C., Koo, J. S. (2008). Growth Suppression of Lung Cancer Cells by Targeting Cyclic AMP Response Element-Binding Protein. Cancer Res. 68: 981-988 [Abstract] [Full Text]  
• Alejandro, E. U., Johnson, J. D. (2008). Inhibition of Raf-1 Alters Multiple Downstream Pathways to Induce Pancreatic -Cell Apoptosis. J. Biol. Chem. 283: 2407-2417 [Abstract] [Full Text]  
• Paroni, G., Fontanini, A., Cernotta, N., Foti, C., Gupta, M. P., Yang, X.-J., Fasino, D., Brancolini, C. (2007). Dephosphorylation and Caspase Processing Generate Distinct Nuclear Pools of Histone Deacetylase 4. Mol. Cell. Biol. 27: 6718-6732 [Abstract] [Full Text]