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Updated: Sep 10, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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A redox switch in p21-CDK feedback during G2 phase controls the proliferation-cell cycle exit decision

Julia Vorhauser1, Theodoros I Roumeliotis2, David Coupe3

  • 1Division of Molecular and Cell Biology, Chester Beatty Laboratories, the Institute of Cancer Research, London SW3 6JB, UK; Cell Cycle, Biotechnology Center (BIOTEC), TU Dresden, 01307 Dresden, Germany.

Molecular Cell
|August 26, 2025
PubMed

Insights

Reactive oxygen species (ROS) modify proteins through S-sulfenylation, impacting cell proliferation. This study identifies a key S-sulfenylation site on p21 that regulates cell cycle progression and stability.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Proteomics

Background:

  • Reactive oxygen species (ROS) are crucial signaling molecules affecting cell proliferation and fate.
  • Oxidation of cysteine residues (S-sulfenylation) is a key mechanism, but specific targets and regulation are unclear.

Purpose of the Study:

  • Identify cell-cycle-coordinated S-sulfenylation events using redox proteomics.
  • Investigate the functional role of S-sulfenylation in controlling cell proliferation.

Main Methods:

  • Redox proteomics to identify S-sulfenylation targets.
  • Analysis of protein oxidation during cell cycle progression.
  • Functional assays to determine the role of S-sulfenylation in p21 regulation.

Main Results:

  • Identified dynamic S-sulfenylation on a subset of cysteines, despite constant overall proteome oxidation.
  • Discovered a critical redox-sensitive cysteine (C41) in p21, a cyclin-dependent kinase (CDK) inhibitor.
  • Demonstrated that C41 oxidation regulates p21 interaction with CDK2/CDK4, controlling p21 stability and cell proliferation post-irradiation.

Conclusions:

  • S-sulfenylation of p21 by ROS is a critical regulatory mechanism for cell cycle control.
  • Oxidation of p21's C41 residue influences its stability and function, impacting cell fate decisions.
  • Suggests a broader coordination between cell cycle progression and redox control through S-sulfenylation of multiple regulators.
Keywords:
CDKN1ACdk2Cdk4G2 phaseROSS-sulfenylationcell cyclecell cycle exitdecision-makingnegative feedback loopoxidationp21proliferationreactive oxygen speciesredoxredox proteomicsredox switchreductionsenescencesulfenic acid

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