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 language | English |
|---|---|
| Pages (from-to) | 2392-2401 |
| Number of pages | 10 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 112 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2011 Sep 1 |
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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 journal › Article
}
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 -