Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion

Jenny Joutsen, Alejandro Jose Da Silva, Jens Christian Luoto, Marek Andrzej Budzynski, Anna Serafia Nylund, Aurelie de Thonel, Jean-Paul Concordet, Valérie Mezger, Délara Sabéran-Djoneidi, Eva Henriksson, Lea Sistonen

Research output: Contribution to journalArticleScientificpeer-review

30 Citations (Scopus)


Maintenance of protein homeostasis, through inducible expression of molecular chaperones, is essential for cell survival under protein-damaging conditions. The expression and DNA-binding activity of heat shock factor 2 (HSF2), a member of the heat shock transcription factor family, increase upon exposure to prolonged proteotoxicity. Nevertheless, the specific roles of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained unknown. Here, we found that HSF2 is critical for cell survival during prolonged proteotoxicity. Strikingly, our RNA sequencing (RNA-seq) analyses revealed that impaired viability of HSF2-deficient cells is not caused by inadequate induction of molecular chaperones but is due to marked downregulation of cadherin superfamily genes. We demonstrate that HSF2-dependent maintenance of cadherin-mediated cell-cell adhesion is required for protection against stress induced by proteasome inhibition. This study identifies HSF2 as a key regulator of cadherin superfamily genes and defines cell-cell adhesion as a determinant of proteotoxic stress resistance.

Original languageEnglish
Pages (from-to)583-597.e6
JournalCell Reports
Issue number2
Publication statusPublished - 14 Jan 2020
MoE publication typeA1 Journal article-refereed


  • Animals
  • Cell Adhesion
  • Cell Death/immunology
  • Cell Survival/immunology
  • Heat Shock Transcription Factors/metabolism
  • Heat-Shock Proteins/metabolism
  • Humans
  • Up-Regulation


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