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YAP accelerates Aβ25–35-induced apoptosis through upregulation of Bax expression by interaction with p73

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Abstract

Accumulation of amyloid-β-peptide (Aβ) in the brain is considered as a pathological hallmark of Alzheimer’s disease (AD). Previous studies show that p73 is vital for mediating the pathogenic process of AD. Yes-associated protein (YAP) has been shown to positively regulate p73 in promoting apoptosis induced by anti-cancer agents. However, the functional role of YAP and potential relationship between YAP and p73 in AD are unknown. In the present study, we found that YAP accelerated apoptosis in response to Aβ25–35 and the nuclear translocation of YAP was involved in cellular signals that regulated the apoptosis. Aβ25–35 induced YAP translocation from cytoplasm to nucleus accompanied with the increased phosphorylation on Y357, resulting in the enhancement of interaction between YAP and p73. Moreover, inhibition of YAP expression by small hairpin RNA (shRNA) suppressed apoptosis induced by Aβ25–35. More importantly, p73-mediated induction of Bax expression and activation were in a YAP-dependent manner. Overexpression of YAP accelerated Bax translocation, upregulated Bax expression and promoted caspase-3 activation. Taken together, our findings first demonstrated that YAP accelerated Aβ-induced apoptosis through nucleus translocation, leading to the induction of Bax expression and activation. Our results provided a potential therapeutic strategy for the treatment of AD through inhibiting YAP/p73/Bax pathway.

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Acknowledgments

This research is supported by the National Basic Research Program of China (2011CB910402; 2010CB732602), the Program for Changjiang Scholars and Innovative Research Team in University (IRT0829), and the National Natural Science Foundation of China (30870676; 30870658). We thank Prof. Subham Basu in Cell Survival Signalling Laboratory Centre for Molecular Oncology and Imaging Barts and The London School of Medicine and Dentistry, John Vane Science Centre, London, UK and Prof. Julian Downward, in Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK for kindly providing the plasmid GFP–YAP, and thank Prof. Hedeki Shimodaira in Department of Clincial Oncology Institute of Development, Aging and Cancer Tohoku University, Japan for kindly providing the plasmid YFP–p73, and thank Prof. Andrew P. Gilmore in Wellcome Trust Centre for Cell Matrix Research, School of Biological Sciences, University of Manchester, Manchester for kindly providing the YFP–Bax plasmid.

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  1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China

    Heng Zhang, Shengnan Wu & Da Xing

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  1. Heng Zhang
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Correspondence to Da Xing.

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Zhang, H., Wu, S. & Xing, D. YAP accelerates Aβ25–35-induced apoptosis through upregulation of Bax expression by interaction with p73. Apoptosis 16, 808–821 (2011). https://doi.org/10.1007/s10495-011-0608-y

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