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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Joutsen J, Da Silva AJ, Luoto JC, Budzynski MA, Nylund AS, de Thonel A, Concordet JP, Mezger V, Sabéran-Djoneidi D, Henriksson E, Sistonen L
Publication year: 2020
Journal: Cell Reports
Volume number: 30
Issue number: 2
Start page: 583
End page: 597


Abstract

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.


Last updated on 2020-14-07 at 06:26