The regulation of apoptosis by the downstream regulatory element antagonist modulator/potassium channel interacting protein 3 (DREAM/KChIP3) through interactions with hexokinase I
Copyright policy )The regulation of apoptosis by the downstream regulatory element antagonist modulator/potassium channel interacting protein 3 (DREAM/KChIP3) through interactions with hexokinase I
The EF-hand protein, DREAM/KChIP3 (henceforth referred to as DREAM), regulates apoptosis by incompletely understood mechanisms. We demonstrate that in the presence of Ca2+, DREAM interacts with hexokinase I, a protein known to bind mitochondria and regulate apoptosis. A mutant DREAM protein construct incapable of binding Ca2+ does not associate with hexokinase I. The amino-terminal portion of DREAM is required for binding to hexokinase I, as a DREAM construct lacking the first 94 amino terminal residues fails to bind hexokinase I. Expression of DREAM in neuroblastoma cells enhances cisplatin mediated caspase-3 activity. Simultaneous expression of hexokinase I in such cells reduces DREAM-stimulated apoptosis. DREAM overexpression in neuroblastoma cells reduces hexokinase I localization on isolated mitochondria. The interaction of DREAM with hexokinase I may be important in the regulation of neuronal apoptosis.
- Mayo Clinic United States
Caspase 3, Blotting, Western, Apoptosis, Kv Channel-Interacting Proteins, Mitochondria, Protein Structure, Tertiary, Enzyme Activation, Gene Expression Regulation, Neoplastic, Mitochondrial Proteins, Mice, Neuroblastoma, Cell Line, Tumor, Hexokinase, Protein Interaction Mapping, Animals, Calcium, Cisplatin, Glycolysis, Edetic Acid, Protein Binding
Caspase 3, Blotting, Western, Apoptosis, Kv Channel-Interacting Proteins, Mitochondria, Protein Structure, Tertiary, Enzyme Activation, Gene Expression Regulation, Neoplastic, Mitochondrial Proteins, Mice, Neuroblastoma, Cell Line, Tumor, Hexokinase, Protein Interaction Mapping, Animals, Calcium, Cisplatin, Glycolysis, Edetic Acid, Protein Binding
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