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

Cell Rep. 2020 Jan 14;30(2):583-597.e6. doi: 10.1016/j.celrep.2019.12.037.


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.

Keywords: Bortezomib; cadherins; cell adhesion; cell survival; heat shock factor; proteotoxic stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Heat Shock Transcription Factors
  • Heat-Shock Proteins