Inositol Hexakisphosphate Kinase 2 Mediates Growth Suppressive and Apoptotic Effects of Interferon-β in Ovarian Carcinoma Cells*

Bei H. Morrison,J. A. Bauer,D. Kalvakolanu,D. Lindner

Published 2001 in Journal of Biological Chemistry

ABSTRACT

Interferons (IFNs) regulate the expression of genes that mediate their antiviral, antitumor, and immunomodulatory actions. We have previously shown that IFN-β suppresses growth of human ovarian carcinoma xenografts in vivo and induces apoptosis of ovarian carcinoma cells in vitro. To investigate mechanisms of IFN-β-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-β in ovarian carcinoma cells. A mutant IP6K2 with substitutions in the putative inositol phosphate binding domain abrogates IFN-β-induced apoptosis. These studies identify a novel function for IP6K2 in cell growth regulation and apoptosis.

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