Involvement of caspase-2 activation in aurora kinase inhibitor-induced cell death in axin-expressing L929 cells
- Authors
- Choi, Eun-Jin; Kim, Shi-Mun; Shin, Jee-Hye; Kim, Sewon; Song, Ki-Joon; Kee, Sun-Ho
- Issue Date
- Apr-2014
- Publisher
- SPRINGER
- Keywords
- Axin; Wnt signaling; Aurora kinase; Caspase-2
- Citation
- APOPTOSIS, v.19, no.4, pp.657 - 667
- Indexed
- SCIE
SCOPUS
- Journal Title
- APOPTOSIS
- Volume
- 19
- Number
- 4
- Start Page
- 657
- End Page
- 667
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/98914
- DOI
- 10.1007/s10495-013-0951-2
- ISSN
- 1360-8185
- Abstract
- Axin is a multifunctional protein that participates in many cellular events including Wnt signaling and cell fate determination. Aurora kinase inhibitor (AKI)-induced cell death and cell membrane rupture is facilitated in L929 cells expressing axin (L-axin cells) through the activation of poly ADP-ribose polymerase (PARP). We observed that caspase-2 activity is required for AKI-induced cell death. Inhibition of caspase-2 activity suppressed AKI-induced PARP activation and mitochondrial dysfunction, resulting in a decrease in AKI-induced cell death. When an axin mutant deleted for the glycogen synthase kinase 3 beta (GSK3 beta)-binding domain was expressed in L929 cells (L-Delta GSK cells), AKI-induced caspase-2 activation and cell death decreased. AKI treatment reduced the expression of a 32-kDa caspase-2 splicing variant (caspase-2S) in most L-axin cells, but not in L-Delta GSK cells. These results suggest that AKI-induced caspase-2 activation in L-axin cells might be due to a decrease in the expression of caspase-2S, which inhibits caspase-2 activity. In addition, AKI treatment failed to activate caspase-8 and treatment with necrostatin inhibited AKI-induced cell death in L-axin cells, suggesting that the absence of caspase-8 activation might favor necrotic cell death. Axin expression may facilitate AKI-induced caspase-2 activation followed by activation of PARP and initiation of the necrotic cell death pathway.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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