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Updated: Nov 18, 2025

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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Roles of CNC Transcription Factors NRF1 and NRF2 in Cancer

Hiroki Sekine1, Hozumi Motohashi1

  • 1Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.

Cancers
|February 4, 2021
PubMed

Insights

Cancer cells exploit metabolism for survival. Transcription factors NRF2 and NRF1 promote cancer malignancy and drug resistance, respectively, through metabolic reprogramming and proteasome activity regulation.

Area of Science:

  • Cellular metabolism
  • Cancer biology
  • Molecular oncology

Background:

  • Cancer cells utilize unique metabolic pathways for survival and proliferation.
  • Nuclear factor erythroid 2-like 2 (NRF2) activation promotes cancer malignancy and therapeutic resistance via metabolic reprogramming.
  • Nuclear factor erythroid 1 (NRF1) contributes to cancer drug resistance by maintaining proteasome activity.

Purpose of the Study:

  • To review NRF2-mediated cancer malignancy.
  • To elaborate on NRF1-mediated drug resistance influenced by UDP-GlcNAc.

Main Methods:

  • Literature review focusing on NRF2 and NRF1 functions in cancer.
  • Analysis of metabolic reprogramming in cancer cells.
  • Examination of the role of UDP-GlcNAc in NRF1 activation.

Main Results:

  • NRF2 activation enhances cancer cell tumorigenesis and resistance.
  • NRF1 protects cancer cells from proteasome inhibitor toxicity.
  • UDP-GlcNAc, generated via the hexosamine pathway, activates NRF1.

Conclusions:

  • Cancer cell metabolic signatures are linked to CNC family member functions.
  • NRF2 and NRF1 play critical roles in cancer progression and therapeutic resistance.
  • Targeting NRF1 and UDP-GlcNAc metabolism may offer strategies for overcoming cancer drug resistance.
Keywords:
CNC proteinsNRF1NRF2O-GlcNAcylationproteasome

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