Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2
- 24 January 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (6), 2205-2209
- https://doi.org/10.1073/pnas.1019381108
Abstract
The inositol pyrophosphate, diphosphoinositol pentakisphosphate, regulates p53 and protein kinase Akt signaling, and its aberrant increase in cells has been implicated in apoptosis and insulin resistance. Inositol hexakisphosphate kinase-2 (IP6K2), one of the major inositol pyrophosphate synthesizing enzymes, mediates p53-linked apoptotic cell death. Casein kinase-2 (CK2) promotes cell survival and is upregulated in tumors. We show that CK2 mediated cell survival involves IP6K2 destabilization. CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation. IP6K2 mutants at the CK2 sites that are resistant to CK2 phosphorylation are metabolically stable.Keywords
This publication has 32 references indexed in Scilit:
- Inositol Pyrophosphates Inhibit Akt Signaling, Thereby Regulating Insulin Sensitivity and Weight GainCell, 2010
- p53-mediated apoptosis requires inositol hexakisphosphate kinase-2Proceedings of the National Academy of Sciences of the United States of America, 2010
- Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathwayProceedings of the National Academy of Sciences of the United States of America, 2010
- Diphosphoinositol Polyphosphates: Metabolic Messengers?Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2009
- Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinomaOncogene, 2009
- Structural Analysis and Detection of Biological Inositol Pyrophosphates Reveal That the Family of VIP/Diphosphoinositol Pentakisphosphate Kinases Are 1/3-KinasesJournal of Biological Chemistry, 2009
- HSP90 regulates cell survival via inositol hexakisphosphate kinase-2Proceedings of the National Academy of Sciences of the United States of America, 2008
- Effect of Inositol Hexakisphosphate Kinase 2 on Transforming Growth Factor β-activated Kinase 1 and NF-κB ActivationPublished by Elsevier BV ,2007
- Regulation of a Cyclin-CDK-CDK Inhibitor Complex by Inositol PyrophosphatesScience, 2007
- Protein kinase CK2 phosphorylates and upregulates Akt/PKBCell Death & Differentiation, 2005