Induction of Herpud1 expression by ER stress is regulated by Nrf1

FEBS Lett. 2015 Feb 27;589(5):615-20. doi: 10.1016/j.febslet.2015.01.026. Epub 2015 Jan 28.

Abstract

Herpud1 is an ER-localized protein that contributes to endoplasmic reticulum (ER) homeostasis by participating in the ER-associated protein degradation pathway. The Nrf1 transcription factor is important in cellular stress pathways. We show that loss of Nrf1 function results in decreased Herpud1 expression in cells and liver tissues. Expression of Herpud1 increases in response to ER stress, but not in Nrf1 knockout cells. Transactivation studies show that Nrf1 acts through antioxidant response elements located in the Herpud1 promoter, and chromatin immunoprecipitation demonstrates that Herpud1 is a direct Nrf1 target gene. These results indicate that Nrf1 is a transcriptional activator of Herpud1 expression during ER stress, and they suggest Nrf1 is a key player in the regulation of the ER stress response in cells.

Keywords: ER stress; Nuclear factor erythroid-derived 2-related factor 1; Transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Endoplasmic Reticulum Stress
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nuclear Respiratory Factor 1 / genetics
  • Nuclear Respiratory Factor 1 / metabolism*
  • Promoter Regions, Genetic / genetics
  • Real-Time Polymerase Chain Reaction
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology

Substances

  • HERPUD1 protein, human
  • Membrane Proteins
  • Nuclear Respiratory Factor 1