The integrated stress response and proteotoxicity in cancer therapy

Research output: Contribution to journalReview article

Abstract

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
Volume482
Issue number3
DOIs
StatePublished - Jan 15 2017

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The integrated stress response and proteotoxicity in cancer therapy'. Together they form a unique fingerprint.

  • Cite this