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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: 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
Publiceringsår: 2020
Tidskrift: Cell Reports
Volym: 30
Nummer: 2
Artikelns första sida, sidnummer: 583
Artikelns sista sida, sidnummer: 597


Abstrakt

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.


Senast uppdaterad 2020-07-07 vid 03:50