Abstract
Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis.
Original language | English |
---|---|
Pages (from-to) | 735–749 |
Number of pages | 15 |
Journal | Journal of Cell Biology |
Volume | 206 |
Issue number | 6 |
DOIs | |
Publication status | Published - 15 Sept 2014 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Animals
- Apoptosis/genetics
- Cell Line, Tumor
- Cell Survival
- Chromatin/genetics
- DNA-Binding Proteins/genetics
- Gene Expression Regulation
- HSP70 Heat-Shock Proteins/biosynthesis
- HeLa Cells
- Heat Shock Transcription Factors
- Heat-Shock Proteins/biosynthesis
- Heat-Shock Response/genetics
- Humans
- MCF-7 Cells
- Mice
- Mitosis/genetics
- Mitotic Index
- RNA Interference
- RNA Polymerase II/genetics
- RNA, Messenger/biosynthesis
- RNA, Small Interfering
- Transcription Factors/biosynthesis
- Transcription, Genetic