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Updated: Aug 31, 2026

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
07:02

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy

Published on: December 16, 2021

Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites

Ahmad L Subhi1, Paula Diegelman, Carl W Porter

  • 1Divisions of Population Science and Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

The Journal of Biological Chemistry
|September 25, 2003
PubMed

Insights

Products of the methionine salvage pathway, including methylthioadenosine phosphorylase (MTAP), inhibit the cancer-promoting enzyme ornithine decarboxylase (ODC). MTAP deletion in tumors may activate ODC, increasing polyamine levels.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Methylthioadenosine phosphorylase (MTAP) is a tumor suppressor gene often deleted in human cancers.
  • Ornithine decarboxylase (ODC) overexpression is common in tumors and promotes tumorigenesis.
  • A potential link between the methionine salvage pathway and polyamine biosynthesis in cancer is suggested.

Purpose of the Study:

  • To investigate a novel regulatory pathway where methionine salvage pathway products inhibit ODC activity.
  • To determine if MTAP deletion contributes to ODC activation in human tumors.
  • To identify key compounds in the methionine salvage pathway that regulate polyamine biosynthesis.

Main Methods:

  • Utilized Saccharomyces cerevisiae to identify the gene encoding MTAP (MEU1).
  • Analyzed ODC activity and polyamine levels in yeast mutants and human tumor cell lines (MCF-7).
  • Assessed the effect of 4-methylthio-2-oxobutanoic acid and MTAP expression on ODC activity and polyamine levels.

Main Results:

  • Meu1Δ yeast cells exhibited an 8-fold increase in ODC activity and elevated polyamine pools.
  • Mutations in downstream salvage pathway genes also led to increased ODC activity and polyamines.
  • 4-methylthio-2-oxobutanoic acid repressed ODC levels in both yeast and human cells.
  • MTAP expression in MTAP-deleted MCF-7 cells significantly reduced ODC activity and polyamine levels.

Conclusions:

  • Products of the methionine salvage pathway negatively regulate polyamine biosynthesis by inhibiting ODC activity.
  • MTAP deletion in human tumors may lead to ODC activation and increased polyamine levels, contributing to tumorigenesis.
  • This pathway represents a potential therapeutic target for cancers with MTAP deletion.

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