Transcription factors Hsf1 and Nrf2 engage in crosstalk for cytoprotection

Sharadha Dayalan Naidu, Rumen V. Kostov, Albena T. Dinkova-Kostova (Lead / Corresponding author)

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Abstract

Transcription factors heat shock factor (Hsf)1 and nuclear factor-erythroid 2 p45-related factor (Nrf)2 are critical for adaptation and survival. Each is maintained at low basal levels, but is robustly activated by various stimuli, including cysteine-reactive small molecules (inducers). Although each is regulated by distinct mechanisms, it is emerging that these transcription factors engage in crosstalk by sharing overlapping transcriptional targets, such as heat shock protein (HSP)70, p62, and activating transcription factor (ATF)3, and in certain cases, compensating for each other. Critically, activation of Hsf1 or Nrf2 affects the cellular redox balance by promoting the reduced state. Conversely, deletion of Hsf1 or Nrf2 is associated with oxidative stress and impaired mitochondrial function. Transient activation of Hsf1 and Nrf2 is cytoprotective, but their persistent upregulation may be detrimental, causing cardiomyopathy or accelerating carcinogenesis, and should be considered when designing strategies for disease prevention and treatment.

Original languageEnglish
Pages (from-to)6-14
Number of pages9
JournalTrends in Pharmacological Sciences
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 2015

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Keywords

  • cysteine reactivity
  • glutathione
  • heat shock
  • Kelch-like ECH associated protein 1 (Keap1)
  • mitochondrial function
  • redox

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