Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells.

Abstract

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.

• Authors: B H Morrison, J A Bauer, D V Kalvakolanu, D J Lindner
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 27 Pg. 24965-70 (Jul 06 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11337497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Isoenzymes
• Oligonucleotides, Antisense
• RNA, Messenger
• Interferon-beta
• Phosphotransferases (Phosphate Group Acceptor)
• inositol hexakisphosphate kinase

Topics

• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Consensus Sequence
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interferon-beta (pharmacology)
• Isoenzymes (metabolism)
• Oligonucleotides, Antisense (pharmacology)
• Ovarian Neoplasms (pathology)
• Phosphotransferases (Phosphate Group Acceptor) (genetics, metabolism)
• RNA, Messenger (metabolism)
• Tumor Cells, Cultured