The acetyltransferase p300 regulates NRF2 stability and localization

Biochem Biophys Res Commun. 2020 Apr 16;524(4):895-902. doi: 10.1016/j.bbrc.2020.02.006. Epub 2020 Feb 10.


The transcription factor NRF2 plays a key role in the protection against environmental stress and maintaining cellular homeostasis. The acetyltransferase p300 is a known component of the NRF2 transcriptional complex and promotes its transcriptional activity. In this study we describe a novel mechanism by which p300 facilitates NRF2 activity. p300 physically interacts with NRF2 and interferes with NRF2-KEAP1 complex formation. In particular, p300 increases NRF2 protein abundance and stability, thereby promoting NRF2 nuclear localization. Notably, the acetyltransferase activity of p300 was indispensable for the stabilizing effects towards NRF2. Furthermore, overexpression of p300 protected HEK293T cells from oxidative stress and increased viability. Together our study uncovers a link between p300 and control of NRF2-KEAP1 signaling via regulation of NRF2 stability and this may act as a novel checkpoint on the adaptation to oxidative stress.

Keywords: NRF2; Nuclear localization; Oxidative stress; Protein stabilization; p300.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Kelch-Like ECH-Associated Protein 1 / genetics*
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Protein Binding
  • Protein Stability
  • Protein Transport
  • Signal Transduction
  • Transcription, Genetic
  • p300-CBP Transcription Factors / deficiency
  • p300-CBP Transcription Factors / genetics*


  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Hydrogen Peroxide
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor