DAP-5 is involved in MycN/IFNgamma-induced apoptosis in human neuroblastoma cells.
Death associated protein-5 (DAP-5) is a ubiquitously expressed member of the translation initiation factor eIF4G family that lacks the eIF4E binding site. A dominant negative fragment of DAP-5 protects HeLa cells from IFNgamma-induced cell death. By employing a functional approach we examined the role of DAP-5 in human neuroblastoma cells that are sensitized for IFNgamma-induced apoptosis by tetracycline controlled MYCN expression. DAP-5 fragment transcribed at high levels and translated into a functional miniprotein of 28 kDa protected neuroblastoma cells from IFNgamma-induced apoptosis. Reduced serum levels were toxic to cells constitutively expressing DAP-5 fragment suggesting that DAP-5 protein is essential for both viability and death of human neuroblastoma cells.
Wittke
I
I
Department of Cytogenetics-H0400, German Cancer Research Center, Im Neuenheimer Feld 280, D 69120, Heidelberg, Germany.
Mädge
B
B
Wiedemeyer
R
R
Kimchi
A
A
Schwab
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D039603:Eukaryotic Initiation Factor-4G; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; C491300:EIF4G2 protein, human; D019309:Epstein-Barr Virus Nuclear Antigens; D039603:Eukaryotic Initiation Factor-4G; D010446:Peptide Fragments; D011506:Proteins; D007371:Interferon-gamma; D001616:beta-Galactosidase; D013752:Tetracycline; C417029:EBV-encoded nuclear antigen 1