Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells.
Interferons (IFNs) regulate the expression of genes that mediate their antiviral, antitumor, and immunomodulatory actions. We have previously shown that IFN-beta suppresses growth of human ovarian carcinoma xenografts in vivo and induces apoptosis of ovarian carcinoma cells in vitro. To investigate mechanisms of IFN-beta-induced apoptosis we employed an antisense technical knockout approach to identify gene products that mediate cell death and have isolated several regulators of interferon-induced death (RIDs). In this investigation, we have characterized one of the RIDs, RID-2. Sequence analysis revealed that RID-2 was identical to human inositol hexakisphosphate kinase 2 (IP6K2). IP6K2 is post-transcriptionally induced by IFN-beta in ovarian carcinoma cells. A mutant IP6K2 with substitutions in the putative inositol phosphate binding domain abrogates IFN-beta-induced apoptosis. These studies identify a novel function for IP6K2 in cell growth regulation and apoptosis.
Morrison
B H
BH
Department of Cancer Biology, Lerner Research Institute, Center for Cancer Drug Development and Discovery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Bauer
J A
JA
Kalvakolanu
D V
DV
Lindner
D J
DJ
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016384:Consensus Sequence; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000473:pathology*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016899:Interferon-beta; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase