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Biochem Biophys Res Commun. 2008 Dec 12;377(2):508-511. doi: 10.1016/j.bbrc.2008.10.021. Epub 2008 Oct 16.

Up-regulation of IAPs by PI-3K: a cell survival signal-mediated anti-apoptotic mechanism.

Author information

1
Department of Life Science, Kyungwon University, 65 Bokjung-dong, Sujeong-gu, Seongnam-si, Kyeonggi-do 461-701, Republic of Korea; Gachon BioNano Research Institute, Kyungwon University, 65 Bokjung-dong, Sujeong-gu, Seongnam-si, Kyeonggi-do 461-701, Republic of Korea; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: seold@kyungwon.ac.kr.

Abstract

Under normal cell physiology, a balance between cell survival and apoptosis is crucial for homeostasis. Many studies have demonstrated that apoptosis is modulated by cell survival stimuli. Active Akt, a common mediator of cell survival signals, has been shown to inhibit apoptosis by attenuating activity of pro-apoptotic factors Bad and caspase-9. However, the anti-apoptotic mechanisms mediated by various cell survival signals are poorly understood. Human prostate cancer LNCaP cells, known to contain constitutively activated Akt as a result of a frame-shift mutation in PTEN, an inhibitor of PI-3K/Akt pathway, were observed to be completely resistant to TRAIL-induced apoptosis. In agreement with the known action of Akt, blockade of the PI-3K/Akt pathway rendered LNCaP cells highly susceptible to TRAIL. Importantly, active PI-3K/Akt prevented processing/activation of caspase-3, a phenomenon associated with the function of inhibitor of apoptosis proteins (IAPs). In fact, inhibition of PI-3K activity using Wortmannin significantly decreased the protein levels of IAPs, concomitantly promoting processing/activation of caspase-3 and TRAIL-induced apoptosis. My data indicate that in addition to blocking Bad and caspase-9 through Akt, PI-3K also inhibits caspase-3 through up-regulating IAPs, thereby attenuates apoptosis.

PMID:
18929542
DOI:
10.1016/j.bbrc.2008.10.021
[Indexed for MEDLINE]

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