Phenylbutyric acid induces the cellular senescence through an Akt/p21 WAF1 signaling pathway

Hag Dong Kim, Chang Young Jang, Jeong Min Choe, Jeongwon Sohn, Joon Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21 WAF1 induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21 WAF1 pathway by PERK inhibition.

Original languageEnglish
Pages (from-to)213-218
Number of pages6
JournalBiochemical and biophysical research communications
Volume422
Issue number2
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • Akt
  • Cellular senescence
  • ER stress
  • PBA
  • PERK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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