Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells.
Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation.
Curtin
J F
JF
Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland.
Cotter
T G
TG
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000494:pharmacology; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases