title: YAP accelerates Aβ(25-35)-induced apoptosis through upregulation of Bax expression by interaction with p73.
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 Aβ(25-35) and the nuclear translocation of YAP was involved in cellular signals that regulated the apoptosis. Aβ(25-35) 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 Aβ(25-35). 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.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C509425:Yap1 protein, rat; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D053148:Caspase 3