CREB-binding protein (CBP) regulates beta-adrenoceptor (beta-AR) - mediated apoptosis
- Author(s)
- Lee, YY; Moujalled, D; Doerflinger, M; Gangoda, L; Weston, R; Rahimi, A; de Alboran, I; Herold, M; Bouillet, P; Xu, Q; Gao, X; Du, XJ; Puthalakath, H;
- Details
- Publication Year 2013-07,Volume 20,Issue #7,Page 941-952
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- Abstract
- Catecholamines regulate the beta-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the beta-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- FAMILY-MEMBER BIM; KINASE-A; CYCLIC-AMP; BETA(2)-ADRENERGIC RECEPTORS; HEART-FAILURE; CELL LYMPHOMA; B-CELLS; STRESS; ACTIVATION; EXPRESSION
- Research Division(s)
- Molecular Genetics Of Cancer
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679460/
- Publisher's Version
- https://doi.org/10.1038/cdd.2013.29
- Terms of Use/Rights Notice
- © 2013 ADMC Associazione Differenziamento e Morte Cellulare
Creation Date: 2013-07-01 12:00:00