Journal article
CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)-mediated apoptosis
YY Lee, D Moujalled, M Doerflinger, L Gangoda, R Weston, A Rahimi, I De Alboran, M Herold, P Bouillet, Q Xu, X Gao, XJ Du, H Puthalakath
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2013
DOI: 10.1038/cdd.2013.29
Abstract
Catecholamines regulate the β-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 β-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 transcr..
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Awarded by CRC Health Group
Funding Acknowledgements
We thank Vishy Iyer, Andreas Strasser, Liam O'Connor, Daniel Gray, Holly Anderton, Diep Chau, Lorraine O'Reilly, Hua Gu and Warren Alexander for reagents and advice. YYL and LG are supported by CRC BT, X-JD is supported by NHMRC project grant (APP1005329) and HP is supported by ARC Future Fellowship (FT0990683) and by ARC project grant (DP110100417).