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Updated: Oct 12, 2025

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Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation

Simone Di Sanzo1, Katrin Spengler2, Anja Leheis2

  • 1Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), 07745, Jena, Germany.

Nature Communications
|November 19, 2021
PubMed

Insights

Advanced glycation end products, like carboxymethyllysine, accumulate with age and disease. This study identifies over 1000 modification sites, revealing impacts on protein function and cellular health.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Proteomics

Background:

  • Posttranslational modifications regulate protein function.
  • Advanced glycation end products (AGEs) accumulate during aging and disease.
  • Specific protein targets and functional consequences of AGEs are largely unknown.

Purpose of the Study:

  • To identify sites of carboxymethyllysine (CML) modification, a major AGE.
  • To investigate the functional consequences of CML modification in cellular systems.
  • To explore the impact of glycation on cellular proteostasis and dynamics.

Main Methods:

  • Proteomic strategy to identify CML modification sites.
  • Quantitative proteomics in mouse and human cells treated with glyoxal.
  • Analysis of cellular responses including proteotoxicity, cell cycle, and microtubule dynamics.

Main Results:

  • Over 1000 sites of protein carboxymethylation identified.
  • Protein glycation triggers a proteotoxic response and affects protein degradation.
  • Glyoxal treatment perturbs cell cycle and impairs microtubule dynamics via CML modification in endothelial cells.

Conclusions:

  • CML modification is relevant to cellular function.
  • Specific protein networks are compromised by glycation during aging.
  • This study provides insights into the molecular mechanisms underlying age-associated cellular dysfunction.

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