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Updated: Jul 27, 2025

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

Published on: July 26, 2019

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Phosphoinositide and redox dysregulation by the anticancer methylthioadenosine phosphorylase transition state

Timothy Salita1, Yepy H Rustam2, Vinzenz Hofferek3

  • 1School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand; Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Australia.

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
|June 10, 2023
PubMed

Insights

Methylthio-DADMe-immucillin-A (MTDIA) inhibits 5'-methylthioadenosine phosphorylase (MTAP), impacting cancer cell lipidomes. This study reveals MTDIA alters lipid signaling and immune responses, suggesting a novel therapeutic mechanism.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Metabolomics

Background:

  • 5'-methylthioadenosine phosphorylase (MTAP) is implicated in cancer progression.
  • MTAP inhibition is a potential anti-cancer therapeutic strategy.
  • S-adenosylmethionine (SAM), salvaged by MTAP, is crucial for lipid metabolism.

Purpose of the Study:

  • To investigate the effects of the MTAP inhibitor Methylthio-DADMe-immucillin-A (MTDIA) on cellular lipidomes.
  • To identify lipidomic changes associated with MTAP inhibition.
  • To explore the downstream consequences of MTDIA-induced lipid alterations.

Main Methods:

  • Lipid profiling of MTDIA-treated Saccharomyces cerevisiae using ultra-high resolution accurate mass spectrometry (UHRAMS).
  • Analysis of lipidomic changes upon MTAP inhibition and MTAP gene knockout.
  • Validation of the phosphoinositide kinase/phosphatase signaling network alterations.

Main Results:

  • MTDIA treatment and MTAP knockout induced global lipidomic changes in yeast.
  • Specific alterations in lipids involved in cell signaling, particularly the phosphoinositide pathway, were observed.
  • Dysregulated lipid metabolism correlated with decreased reactive oxygen species (ROS) and modulated immune response factors in mammalian cells.

Conclusions:

  • MTDIA significantly alters cellular lipid homeostasis.
  • MTAP inhibition affects lipid signaling networks, impacting cellular functions.
  • Lipidomic alterations may contribute to the anti-cancer efficacy of MTDIA.
Keywords:
Cancer therapeuticsLipid metabolismLipidomicsMass spectrometryPhosphoinositideTransition-state analog

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