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Title 

Expression of αb-crystallin overrides the anti-apoptotic activity of XIAP

Authors 

J S LeeH Y KimN Y JeongS Y LeeY G YoonY H ChoiC YanIn-Sun ChuH KohH T ParkY H Yoo

Publisher 

Oxford University Press

Issue Date 

2012

Citation 

Neuro-Oncology, vol. 14, no. 11, pp. 1332-1345

Keywords 

αB-crystallinapoptosisgliomaSAHAXIAP

Abstract 

Although crystallins are major structural proteins in the lens, α-crystallins perform non-lens functions, and αB-crystallin has been shown to act as an anti-apoptotic mediator in various cells. The present study was undertaken to examine whether αB-crystallin expressed in human malignant glioma cells exerts anti-apoptotic acitivity. In addition, we sought to elucidate the mechanism underlying any observed anti-apoptotic function of αB-crystallin in these cells. Three glioma cell lines, U373MG, U118MG, and T98G, were used. We observed that only the U373MG cell line expresses αB-crystallin, whereas the other 2 glioma cell lines, U118MG and T98G, demonstrated no endogenous expression of αB-crystallin. We next observed that the silencing of αB-crystallin sensitized U373MG cells to suberoylanilide hydroxamic acid (SAHA)-induced apoptosis and that αB-crystallin associates with caspase-3 and XIAP. Because XIAP is the most potent suppressor of mammalian apoptosis through the direct binding with caspases, we assessed whether XIAP also plays an anti-apoptotic role in SAHA-induced apoptosis in αB-crystallin-expressing U373MG cells. Of note, the silencing of XIAP did not alter the amount of cell death induced by SAHA, indicating that XIAP does not exert an anti-apoptotic activity in U373MG cells. We then determined whether the ectopic expression of αB-crystallin in glioma cells caused a loss of the anti-apoptotic activity of XIAP. Accordingly, we established 2 αB-crystallin over-expressing glioma cell lines, U118MG and T98G, and found that the silencing of XIAP did not sensitize these cells to SAHA-induced apoptosis. These findings suggest that αB-crystallin expressed in glioma cells overrides the anti-apoptotic activity exerted by XIAP.

ISSN 

1522-8517

Link 

http://dx.doi.org/10.1093/neuonc/nos247

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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