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

Wujing Dai, Han Qu, Jack Zhang, Angkana Thongkum, Thai Nho Dinh, Kyle V. Kappeler, Qin M. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress is ubiquitously involved in disease etiology or progression. While the damaging effects have been well characterized, how cells deal with oxidative stress for prevention or removal of damage remains to be fully elucidated. Works from our laboratory have revealed de novo Nrf2 protein translation when cells are encountering low to mild levels of oxidative stress. Nrf2 encodes a transcription factor controlling a myriad of genes important for antioxidation, detoxification, wound repair and tissue remodeling. Here we report a role of FUBP1 in regulating de novo Nrf2 protein translation. An increase of FUBP1 binding to Nrf2 5′UTR due to H2O2 treatment has been found by LC-MS/MS, Far Western blot and ribonucleoprotein immunoprecipitation assays. Blocking FUBP1 expression using siRNA abolished H2O2 from inducing Nrf2 protein elevation or Nrf2 5′UTR activity. While no nuclear to cytoplasmic translocation was detected, cytosolic redistribution to the ribosomal fractions was observed due to oxidant treatment. The presence of FUBP1 in 40/43S ribosomal fractions confirm its involvement in translation initiation of Nrf2 protein. When tested by co-immunoprecipitation with eIF4E, eIF2a, eIF3η and eIF1, only eIF3η was found to gain physical interaction with FUBP1 due to H2O2 treatment. Our data support a role of FUBP1 for promoting the attachment of 40S ribosomal subunit to Nrf2 mRNA and formation of 43S pre-initiation complex for translation initiation of Nrf2 protein under oxidative stress.

Original languageEnglish (US)
Article number101906
JournalRedox Biology
Volume41
DOIs
StatePublished - May 2021

Keywords

  • 5′UTR
  • Initiation factors
  • Oxidative stress
  • Protein translation
  • RNA binding Protein

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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