Hsp90-mediated inhibition of FKBP38 regulates apoptosis in neuroblastoma cells.
The FK506-binding protein 38 (FKBP38) is a pro-apoptotic regulator of Bcl-2 in neuroblastoma cells. Hsp90 inhibits the pro-apoptotic FKBP38/CaM/Ca(2+) 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.
Max-Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120, Halle/Saale, Germany.
Frank
F
Erdmann
Franziska
F
Jarczowski
Matthias
M
Weiwad
Gunter
G
Fischer
Frank
F
Edlich
D017209:Apoptosis; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019807:Iodoacetic Acid / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002147:Calmodulin; D018841:HSP90 Heat-Shock Proteins; D022021:Tacrolimus Binding Proteins; D002118:Calcium; D019807:Iodoacetic Acid