The regulation of apoptosis by the downstream regulatory element antagonist modulator/potassium channel interacting protein 3 (DREAM/KChIP3) through interactions with hexokinase I

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• 作者：Theodore A. Craig^a ; ^b ; ^{rkumar@mayo.edu} ; Pradeep L. Ramachandran^a ; ^b ; H. Robert Bergen 3rd^c ; Jewel L. Podratz^d ; Anthony J. Windebank^d ; Rajiv Kumar^a ; ^b ; ^c
• 关键词：Ca2+ ; calcium ion ; DREAM ; downstream regulatory element antagonist modulator ; KChIP3 ; potassium channel interacting protein ; EDTA ; ethylenediaminetetraacetic acid ; EGTA ; ethylene glycol-bis(2-aminoethylether)-N ; N ; N&prime ; N&prime ; -tetraacetic acid
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：19 April, 2013
• 年：2013
• 卷：433
• 期：4
• 页码：508-512
• 全文大小：442 K

文摘

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.