Hsp90-mediated inhibition of FKBP38 regulates apoptosis in neuroblastoma cells

被引:12
作者
Erdmann, Frank [1 ]
Jarczowski, Franziska [1 ]
Weiwad, Matthias [1 ]
Fischer, Gunter [1 ]
Edlich, Frank [1 ]
机构
[1] Max Planck Unit Enzymol Prot Folding, D-06120 Halle, Germany
关键词
apoptosis; Bcl-2; PPIase; FK506-binding protein; FKBP38;
D O I
10.1016/j.febslet.2007.11.037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The FK506-binding protein 38 (FKBP38) is a proapoptotic regulator of Bcl-2 in neuroblastoma cells. Hsp90 inhibits the pro-apoptotic FKBP38/CaM/Ca2+ complex and thus prevents interactions between FKBP38 and Bcl-2. Here we show that Hsp90 increases cell survival rates of neuroblastoma cells after apoptosis induction. Depletion of FKBP38 by short interference RNA significantly decreased the anti-apoptotic effect of Hsp90 expression. In addition, the influence of high cellular Hsp90 levels was only observed in post-stimulation apoptosis that is sensitive to selective FKBP38 active site inhibition. Similar anti-apoptotic effects in neuroblastoma cells were observed after stimulation of endogenous Hsp90 expression. Hence, the inhibition of FKBP38 by Hsp90 participates in programmed cell death control of neuroblastoma cells. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:5709 / 5714
页数:6
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