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 anti viral, antitumor, and immunomodulatory actions. We have previously shown th at 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 technica l knockout approach to identify gene products that mediate cell death and h ave isolated several regulators of interferon-induced death (RIDs). In this investigation, we have characterized one of the RIDs, RID-2. Sequence anal ysis revealed that RID-2 was identical to human inositol hexakisphosphate k inase 2 (IP6K2). IP6K2 is post-transcriptionally induced by IFN-beta in ova rian carcinoma cells. A mutant IP6K2 with substitutions in the putative ino sitol phosphate binding domain abrogates IFN-beta -induced apoptosis. These studies identify a novel function for IP6K2 in cell growth regulation and apoptosis.