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NRF2 and the Moirai: Life and Death Decisions on Cell Fates

Yoko Yagishita1, Dionysios V Chartoumpekis2, Thomas W Kensler1

  • 1Translational Research Program, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

Antioxidants & Redox Signaling
|December 12, 2022
PubMed

Insights

The transcription factor NRF2 (NF-E2-related factor 2) regulates cellular defense and impacts cell fate. Further research is needed to understand its complex network roles in cell life cycle regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular defense mechanisms.
  • NRF2 activates genes involved in redox balance and xenobiotic detoxification.
  • Emerging evidence links NRF2 to cell fate regulation, influencing cell birth, differentiation, and death.

Purpose of the Study:

  • To explore the expanding roles of NRF2 beyond its canonical cytoprotective functions.
  • To investigate the integration of NRF2 signaling into cell fate determination pathways.
  • To highlight the need for comprehensive studies on NRF2's network interactions.

Main Methods:

  • Comprehensive transcriptional analyses to identify NRF2 target genes.
  • Examination of NRF2's influence on key cellular transition processes.
  • Review of existing evidence on NRF2's association with cell fate regulation.

Main Results:

  • NRF2 target genes encompass both canonical cytoprotective functions and pathways regulating cell fate.
  • NRF2 signaling is molecularly integrated into cell cycle regulation (birth, differentiation, death).
  • The complexity of NRF2's role extends beyond its known detoxifying functions.

Conclusions:

  • A narrow focus on NRF2 signaling alone limits understanding of its role in cell fate determination.
  • Further research is required to explore compensatory downstream pathways and signaling crosstalk.
  • Optimized in vivo models and systems-level approaches are crucial for elucidating NRF2's network capabilities in cell fate regulation.
Keywords:
KEAP1NRF2cell differentiationcell proliferationcell signalingprogramed cell deathstem cells

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