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Role of p53 in cAMP/PKA pathway mediated apoptosis

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Abstract

Deregulated β-adrenoceptor/cAMP-PKA pathway 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. We recently had demonstrated 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. 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 [Lee et al., Cell Death Difference 20(7):941–952 (2013)]. However since CBP is a co-factor for multiple transcription factors, BH-3 only proteins other than Bim could also contribute to this apoptosis pathway. Here we provide evidence for the involvement of p53-CBP axis in apoptosis through Puma/Noxa induction, in response to β-adrenoceptor activation. Our findings highlight the molecular complexity of pathophysiology associated with a deregulated neuro-endocrine system and for developing novel therapeutic strategies for these diseases.

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Acknowledgments

We thank Andreas Strasser and Anissa Jabbour for reagents and advice. HP is supported by ARC Future Fellowship (FT0990683) and by ARC project Grant (DP110100417).

Conflict of interest

The authors declare no conflict of interest

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Authors and Affiliations

  1. Department of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, VIC, 3086, Australia

    Ahmad Rahimi, Ying Ying Lee, Hassen Abdella, Marcel Doerflinger, Lahiru Gangoda, Rahul Srivastava, Kun Xiao & Hamsa Puthalakath

  2. Cell Death Signalling Division, The Walter and Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, VIC, 3050, Australia

    Paul G. Ekert

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  1. Ahmad Rahimi
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  2. Ying Ying Lee
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  9. Hamsa Puthalakath
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Correspondence to Hamsa Puthalakath.

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Rahimi, A., Lee, Y.Y., Abdella, H. et al. Role of p53 in cAMP/PKA pathway mediated apoptosis. Apoptosis 18, 1492–1499 (2013). https://doi.org/10.1007/s10495-013-0895-6

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  • DOI: https://doi.org/10.1007/s10495-013-0895-6

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