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Updated: Jun 5, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

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

Anutosh Chakraborty1, J Kent Werner, Michael A Koldobskiy

  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 26, 2011
PubMed

Insights

Casein kinase-2 (CK2) promotes cell survival by phosphorylating and destabilizing inositol hexakisphosphate kinase-2 (IP6K2), a key enzyme in apoptosis. This phosphorylation enhances IP6K2 degradation, impacting cell death pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Inositol pyrophosphates regulate critical cell signaling pathways, including p53 and Akt.
  • Aberrant levels of diphosphoinositol pentakisphosphate are linked to apoptosis and insulin resistance.
  • Inositol hexakisphosphate kinase-2 (IP6K2) is crucial for p53-mediated apoptosis.
  • Casein kinase-2 (CK2) is a survival-promoting kinase often upregulated in tumors.

Purpose of the Study:

  • To investigate the role of CK2 in regulating IP6K2 stability and its impact on cell survival and apoptosis.
  • To elucidate the molecular mechanism by which CK2 affects IP6K2.

Main Methods:

  • Phosphorylation site analysis of IP6K2 by CK2.
  • Ubiquitination assays.
  • Cellular depletion studies using HCT116 cells.
  • Analysis of IP6K2 mutants resistant to CK2 phosphorylation.

Main Results:

  • CK2 phosphorylates IP6K2 at specific serine residues (S347 and S356) within a PEST sequence.
  • This CK2-mediated phosphorylation enhances IP6K2 ubiquitination and subsequent proteasomal degradation.
  • HCT116 cells lacking IP6K2 exhibit resistance to cell death induced by CK2 inhibitors.
  • Mutants of IP6K2 resistant to CK2 phosphorylation are metabolically stable.

Conclusions:

  • CK2-mediated phosphorylation of IP6K2 is a key mechanism for its destabilization and degradation.
  • This regulatory pathway contributes to CK2-driven cell survival by reducing levels of the pro-apoptotic IP6K2.
  • Targeting the CK2-IP6K2 interaction could offer therapeutic strategies for cancer.

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