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)2392-2401
Number of pages10
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
Publication statusPublished - 2011 Sep 1

Fingerprint

Aurora Kinases
Poly(ADP-ribose) Polymerases
Cell death
Apoptosis Inducing Factor
Cell Death
Chemical activation
Cell membranes
Cytochromes c
Caspase 3
Adenosine Diphosphate
Chromatin
Centrosome
Spindle Apparatus
Polyploidy
Condensation
Adenosine Triphosphate
Apoptosis
Rupture
Cell Membrane
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation. / Choi, Eun Jin; Kim, Shi Mun; Song, Ki-Joon; Lee, Jae Myun; Kee, Sun-Ho.

In: Journal of Cellular Biochemistry, Vol. 112, No. 9, 01.09.2011, p. 2392-2401.

Research output: Contribution to journalArticle

@article{41f6c2412de04864876707fd8810c4eb,
title = "Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation",
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.",
keywords = "AIF, Aurora kinase, Axin, Cell death, PARP",
author = "Choi, {Eun Jin} and Kim, {Shi Mun} and Ki-Joon Song and Lee, {Jae Myun} and Sun-Ho Kee",
year = "2011",
month = "9",
day = "1",
doi = "10.1002/jcb.23162",
language = "English",
volume = "112",
pages = "2392--2401",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation

AU - Choi, Eun Jin

AU - Kim, Shi Mun

AU - Song, Ki-Joon

AU - Lee, Jae Myun

AU - Kee, Sun-Ho

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

KW - AIF

KW - Aurora kinase

KW - Axin

KW - Cell death

KW - PARP

UR - http://www.scopus.com/inward/record.url?scp=84860400051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860400051&partnerID=8YFLogxK

U2 - 10.1002/jcb.23162

DO - 10.1002/jcb.23162

M3 - Article

C2 - 21520248

AN - SCOPUS:84860400051

VL - 112

SP - 2392

EP - 2401

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 9

ER -