Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2

Anutosh Chakraborty, J. Kent Werner, Michael A. Koldobskiy, Asif K. Mustafa, Krishna R. Juluri, Joseph Pietropaoli, Adele M. Snowman, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

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 PESTsequence, 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.

Original languageEnglish (US)
Pages (from-to)2205-2209
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number6
DOIs
StatePublished - Feb 8 2011

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2'. Together they form a unique fingerprint.

Cite this