Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway
Autor: | Jochen H. M. Prehn, D Kögel, Harry Engemann, Claus Reimertz, Karl Heinz Scheidtmann, Monika Poppe, P Mech, M C Frühwald |
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Rok vydání: | 2001 |
Předmět: |
Cancer Research
Programmed cell death Recombinant Fusion Proteins Green Fluorescent Proteins bcl-X Protein PAWR Apoptosis Cytochrome c Group Cysteine Proteinase Inhibitors Protein Serine-Threonine Kinases Mitochondrion Biology medulloblastoma Transfection Amino Acid Chloromethyl Ketones Neuroblastoma Bcl-2 family Tumor Cells Cultured Humans ddc:610 Protein kinase A DAP kinase family Kinase Intracellular Signaling Peptides and Proteins Regular Article Intracellular Membranes Caspase Inhibitors Mitochondria Gene Expression Regulation Neoplastic Death-Associated Protein Kinases Luminescent Proteins Microscopy Fluorescence Proto-Oncogene Proteins c-bcl-2 Oncology Calcium-Calmodulin-Dependent Protein Kinases Mutation Cancer research Signal transduction Dlk/ZIP kinase Apoptosis Regulatory Proteins Carrier Proteins Oligopeptides Signal Transduction |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | Dlk/ZIP kinase is a member of the Death Associated Protein (DAP) kinase family of pro-apoptotic serine/threonine kinases that have been implicated in regulation of apoptosis and tumour suppression. Expression of both Dlk/ZIP kinase and its interaction partner Par-4 is maintained in four medulloblastoma cell lines investigated, whereas three of seven neuroblastoma cell lines have lost expression of Par-4. Overexpression of a constitutively pro-apoptotic deletion mutant of Dlk/ZIP kinase induced significant apoptosis in D283 medulloblastoma cells. Cell death was characterized by apoptotic membrane blebbing, and a late stage during which the cells had ceased blebbing and were drastically shrunken or disrupted into apoptotic bodies. Over-expression of the anti-apoptotic Bcl-xL protein had no effect on Dlk/ZIP kinase-induced membrane blebbing, but potently inhibited Dlk/ZIP kinase-induced cytochrome c release and transition of cells to late stage apoptosis. Treatment with caspase inhibitors delayed, but did not prevent entry into late stage apoptosis. These results demonstrate that Dlk/ZIP kinase-triggered apoptosis involves the mitochondrial apoptosis pathway. However, cell death proceeded in the presence of caspase inhibitors, suggesting that Dlk/ZIP kinase is able to activate alternative cell death pathways. Alterations of signal transduction pathways leading to Dlk/ZIP kinase induced apoptosis or loss of expression of upstream activators could play important roles in tumour progression and metastasis of neural tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com |
Databáze: | OpenAIRE |
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