Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion
Lea Sistonen; Jenny Joutsen; Marek Andrzej Budzynski; Anna Serafia Nylund; Eva Henriksson; Délara Saberan-Djoneidi; Valérie Mezger; Aurelie de Thonel; Alejandro Jose Da Silva; Jens Christian Luoto; Jean-Paul Concordet
Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion
Lea Sistonen
Jenny Joutsen
Marek Andrzej Budzynski
Anna Serafia Nylund
Eva Henriksson
Délara Saberan-Djoneidi
Valérie Mezger
Aurelie de Thonel
Alejandro Jose Da Silva
Jens Christian Luoto
Jean-Paul Concordet
CELL PRESS
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042713304
https://urn.fi/URN:NBN:fi-fe2021042713304
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]