التفاصيل البيبلوغرافية
| العنوان: |
Characterisation of the anti-apoptotic function of survivin-ΔEx3 during TNFα−mediated cell death. |
| المؤلفون: |
Malcles, M.-H., Wang, H.-W., Koumi, A., Tsai, Y.-H., Yu, M., Godfrey, A., Boshoff, C. |
| المصدر: |
British Journal of Cancer; 6/4/2007, Vol. 96 Issue 11, p1659-1666, 8p |
| مصطلحات موضوعية: |
CELL death, APOPTOSIS, CELL division, CANCER, DRUG therapy |
| مستخلص: |
Survivin is an oncogenic protein involved in cell division and acts as an anti-apoptotic factor. It is highly expressed in most cancers and is associated with chemotherapy resistance, increased tumour recurrence, and shorter patient survival. This makes anti-survivin therapy an attractive cancer treatment strategy. These functions are mediated by several survivin spliced variants, whose expression may correlate with cancer progression. One of the spliced variants, survivin-ΔEx3, is known to inhibit apoptosis, through undefined mechanisms. Here, we characterised these mechanisms upon TNFα−mediated apoptosis, and showed that survivin-ΔEx3 acts as an adaptor, allowing the formation of a complex between Bcl-2 and activated caspase-3. The Bcl-2/survivin-ΔEx3 complex, but not survivin-ΔEx3 itself, inhibits the activity of caspase-3. Bcl-2 is therefore linked to the postmitochondrial apoptotic machinery by survivin-ΔEx3. Thus, survivin-ΔEx3 plays a key role in the inhibition of caspase-3 activity, and in the control of the mitochondrial checkpoint of apoptosis. This study suggests that targeting survivin-ΔEx3, rather than survivin alone, could be relevant for treating human cancers.British Journal of Cancer (2007) 96, 1659–1666. doi:10.1038/sj.bjc.6603768 www.bjcancer.com Published online 15 May 2007 [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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