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

Heng Zhang, Shengnan Wu, Da Xing*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)808-821
Number of pages14
JournalApoptosis : an international journal on programmed cell death
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Keywords

  • Alzheimer's disease (AD)
  • Amyloid beta (Aβ)
  • Bax
  • YAP
  • p73

Fingerprint

Dive into the research topics of 'YAP accelerates Aβ25-35-induced apoptosis through upregulation of Bax expression by interaction with p73'. Together they form a unique fingerprint.

Cite this