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Far Upstream Binding Protein 1 (FUBP1) participates in translational regulation of Nrf2 protein under oxidative

Wujing Dai1, Han Qu1, Jack Zhang2

  • 1Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA; Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.

Redox Biology
|March 6, 2021
PubMed

Insights

The protein FUBP1 promotes the translation of Nrf2 (Nuclear factor erythroid 2-related factor 2) under oxidative stress. This mechanism is crucial for cellular defense and antioxidant responses.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Biochemistry

Background:

  • Oxidative stress contributes to disease, but cellular defense mechanisms require further elucidation.
  • The transcription factor Nrf2 (Nuclear factor erythroid 2-related factor 2) is vital for antioxidant and detoxification pathways.
  • Previous work identified de novo Nrf2 protein translation under mild oxidative stress.

Purpose of the Study:

  • To investigate the role of FUBP1 in regulating Nrf2 protein translation during oxidative stress.
  • To elucidate the molecular mechanism by which FUBP1 influences Nrf2 synthesis.

Main Methods:

  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
  • Far Western blot
  • Ribonucleoprotein immunoprecipitation assays
  • Small interfering RNA (siRNA) knockdown
  • Co-immunoprecipitation assays

Main Results:

  • Hydrogen peroxide (H2O2) treatment increased FUBP1 binding to the Nrf2 5' untranslated region (UTR).
  • FUBP1 knockdown abolished H2O2-induced Nrf2 protein elevation and Nrf2 5'UTR activity.
  • FUBP1 redistributed to cytosolic ribosomal fractions and interacted with eIF3η, suggesting a role in translation initiation.
  • FUBP1 facilitates 40S ribosomal subunit attachment to Nrf2 mRNA, promoting 43S pre-initiation complex formation.

Conclusions:

  • FUBP1 is a key regulator of de novo Nrf2 protein translation under oxidative stress.
  • FUBP1's interaction with ribosomal components and translation factors is critical for initiating Nrf2 synthesis.
  • This pathway represents a novel cellular defense mechanism against oxidative damage.
Keywords:
5′UTRInitiation factorsOxidative stressProtein translationRNA binding Protein

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