Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells

Inge M N Wortel, Laurens T van der Meer, Michael S Kilberg, Frank N van Leeuwen

Research output: Contribution to journalReview articlepeer-review

Abstract

Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells. ATF4 controls the expression of a wide range of adaptive genes that allow cells to endure periods of stress, such as hypoxia or amino acid limitation. However, under persistent stress conditions, ATF4 promotes the induction of apoptosis. Recent advances point to a role for post-translational modifications (PTMs) and epigenetic mechanisms in balancing these pro- and anti-survival effects of ATF4. We review here how PTMs and epigenetic modifiers associated with ATF4 may be exploited by cancer cells to cope with cellular stress conditions that are intrinsically associated with tumor growth. Identification of mechanisms that modulate ATF4-mediated transcription and its effects on cellular metabolism may uncover new targets for cancer treatment.

Original languageEnglish
Pages (from-to)794-806
Number of pages13
JournalTrends in endocrinology and metabolism: TEM
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 2017
Externally publishedYes

Keywords

  • Activating Transcription Factor 4/genetics
  • Adaptation, Physiological/genetics
  • Amino Acids/deficiency
  • Animals
  • Apoptosis/genetics
  • Cell Survival/genetics
  • Humans
  • Hypoxia/genetics
  • Neoplasms/genetics
  • Protein Processing, Post-Translational
  • Stress, Physiological/physiology

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