title: The regulation of apoptosis by the downstream regulatory element antagonist modulator/potassium channel interacting protein 3 (DREAM/KChIP3) through interactions with hexokinase I.
abstract: 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.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Craig
authors.forename: Pradeep L
authors.initials: PL
authors.lastname: Ramachandran
authors.forename: H Robert
authors.initials: HR
authors.lastname: Bergen
authors.forename: Jewel L
authors.initials: JL
authors.lastname: Podratz
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004492:Edetic Acid / Q000378:metabolism; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C496756:Csen protein, mouse; D051605:Kv Channel-Interacting Proteins; D024101:Mitochondrial Proteins; D012097:Repressor Proteins; D004492:Edetic Acid; C515658:HK1 protein, mouse; D006593:Hexokinase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D002945:Cisplatin; D002118:Calcium