Transcription Factor NRF2 Participates in Cell Cycle Progression at the Level of G1/S and Mitotic Checkpoints

Diego Lastra1,2,3,4, Maribel Escoll1,2,3,4, Antonio Cuadrado1,2,3,4

  • 1Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), 28029 Madrid, Spain.

Insights

The transcription factor NRF2, crucial for cell protection, plays a role in cell division. NRF2 levels fluctuate during the cell cycle, and its depletion causes cell cycle arrest.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of cytoprotective responses.
  • The involvement of NRF2 in cell division cycle regulation remains underexplored.

Purpose of the Study:

  • To investigate the role of NRF2 in the cell division cycle.
  • To determine NRF2 expression patterns throughout the cell cycle and its impact on cell cycle progression.

Main Methods:

  • Cell synchronization using standard methods.
  • Flow cytometry to monitor cell cycle progression.
  • NRF2 gene knockdown to assess its functional role.
  • Targeted transcriptomics to analyze cell cycle regulator expression.

Main Results:

  • NRF2 levels peak at S phase entry and are lowest during mitosis.
  • NRF2 depletion results in cell cycle arrest at both G1 and M phases.
  • NRF2 knockdown alters the expression of critical cell cycle regulators including CDK2, TFDP1, CDK6, CDKN1A (p21), CDKN1B (p27), CCNG1, and RAD51.

Conclusions:

  • NRF2 is implicated in the regulation of cell cycle progression.
  • NRF2 influences key cell cycle regulators, affecting cell division.
  • This study reveals a novel function of NRF2 in cell cycle dynamics.

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