Projects per year
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.
Original language | English |
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Pages (from-to) | 583-597.e6 |
Journal | Cell Reports |
Volume | 30 |
Issue number | 2 |
DOIs | |
Publication status | Published - 14 Jan 2020 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Animals
- Cell Adhesion
- Cell Death/immunology
- Cell Survival/immunology
- Heat Shock Transcription Factors/metabolism
- Heat-Shock Proteins/metabolism
- Humans
- Up-Regulation
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Dive into the research topics of 'Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion'. Together they form a unique fingerprint.Projects
- 1 Finished
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CellMech: Center of Excellence in Cellular Mechanostasis
Sahlgren, C. (Principal Investigator), Sistonen, L. (Principal Investigator), Eriksson, J. (Principal Investigator), Toivola, D. (Principal Investigator), Meinander, A. (Principal Investigator), Cheng, F. (Principal Investigator) & Jacquemet, G. (Principal Investigator)
01/03/19 → 29/02/24
Project: Foundation