Format

Send to

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

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

Author information

1
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland.
2
CNRS, UMR 7216 "Epigenetic and Cell Fate," 75250 Paris Cedex 13, France; University of Paris Diderot, Sorbonne Paris Cité, 75250 Paris Cedex 13, France; Département Hospitalo-Universitaire DHU PROTECT, Paris, France.
3
INSERM U1154, CNRS UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
4
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland. Electronic address: lea.sistonen@abo.fi.

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.

KEYWORDS:

Bortezomib; cadherins; cell adhesion; cell survival; heat shock factor; proteotoxic stress

PMID:
31940498
DOI:
10.1016/j.celrep.2019.12.037
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center