Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation

Eun Jin Choi, Shi Mun Kim, Ki Joon Song, Jae Myun Lee, Sun Ho Kee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Axin, a negative regulator of Wnt signaling, participates in apoptosis, and Axin1 localizes to centrosomes and mitotic spindles, which requires Aurora kinase activity. In this study, Aurora inhibition of Axin1-expressing cells (L-Axin) produced polyploid cells, which died within 48h posttreatment, whereas Axin2-expressing cells (L-Axin2) survived the same period. These cell death events showed apoptotic signs, such as chromatin condensation and increased sub-G1 populations, as well as cell membrane rupture. Further analysis showed that Aurora kinase inhibitor (AKI) treatment of L-Axin cells induced poly(ADP-ribose) polymerase (PARP) activation, which increased the poly(ADP-ribosyl)ation of cellular proteins and reduced cellular ATP content. PARP inhibition reduced a proportion of dead cells, suggesting PARP involvement in AKI-induced cell death. Also, AKI treatment of L-Axin cells induced mitochondrial apoptosis-inducing factor (AIF) release, but not mitochondrial cytochrome c release or caspase-3 activation. Knockdown of AIF attenuated AKI-induced cell death in L-Axin cells. Thus, our results suggest that Axin1 expression renders L929 cells sensitive to Aurora inhibition-induced cell death in a PARP- and AIF-dependent manner.

Original languageEnglish
Pages (from-to)2392-2402
Number of pages11
JournalJournal of cellular biochemistry
Volume112
Issue number9
DOIs
Publication statusPublished - 2011 Sep

Keywords

  • AIF
  • Aurora kinase
  • Axin
  • Cell death
  • PARP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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