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
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