The integrated stress response and proteotoxicity in cancer therapy

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations


A variety of different forms of cellular stress can cause protein misfolding and aggregation and proteotoxicity. The cytoprotective response to proteotoxicity is termed the integrated stress response and involves 4 distinct serine/threonine protein kinases that converge on the translation initiation factor eIF2α, resulting in phosphorylation at S51, cell cycle arrest, and a general inhibition of global protein synthesis. Phosphorylation of eIF2α also promotes translation of ATF4 and the expression of ATF4 target genes that ameliorate proteotoxic stress but can also promote apoptosis. This mini review provides a general overview of these mechanisms and discusses how the inter-tumor heterogeneity that involves them affects sensitivity and resistance to proteasome inhibitors, a new class of cancer therapeutics that promotes tumor cell killing via proteotoxic stress.

Original languageEnglish (US)
Pages (from-to)450-453
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Jan 15 2017


  • Autophagy
  • ER stress
  • HRI
  • PERK
  • Protein aggregates
  • Translation
  • Unfolded protein response

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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