Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival

Alexandra N. Elsing, Camilla Aspelin, Johanna K. Björk, Heidi A. Bergman, Samu V. Himanen, Marko Kallio, Pia Roos-Mattjus, Lea Sistonen

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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 languageEnglish
Pages (from-to)735-749
JournalJournal of Cell Biology
Volume206
Issue number6
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

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Mitosis
Cell Survival
Heat-Shock Proteins
Apoptosis
Physiological Stress
RNA Polymerase II
Aneuploidy
Chromatin
Shock
Homeostasis
Hot Temperature
Cell Line
Survival
Proteins

Cite this

Elsing, A. N., Aspelin, C., Björk, J. K., Bergman, H. A., Himanen, S. V., Kallio, M., ... Sistonen, L. (2014). Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival. Journal of Cell Biology, 206(6), 735-749. https://doi.org/10.1083/jcb.201402002
Elsing, Alexandra N. ; Aspelin, Camilla ; Björk, Johanna K. ; Bergman, Heidi A. ; Himanen, Samu V. ; Kallio, Marko ; Roos-Mattjus, Pia ; Sistonen, Lea. / Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival. In: Journal of Cell Biology. 2014 ; Vol. 206, No. 6. pp. 735-749.
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Elsing, AN, Aspelin, C, Björk, JK, Bergman, HA, Himanen, SV, Kallio, M, Roos-Mattjus, P & Sistonen, L 2014, 'Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival', Journal of Cell Biology, vol. 206, no. 6, pp. 735-749. https://doi.org/10.1083/jcb.201402002

Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival. / Elsing, Alexandra N.; Aspelin, Camilla; Björk, Johanna K.; Bergman, Heidi A.; Himanen, Samu V.; Kallio, Marko; Roos-Mattjus, Pia; Sistonen, Lea.

In: Journal of Cell Biology, Vol. 206, No. 6, 2014, p. 735-749.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival

AU - Elsing, Alexandra N.

AU - Aspelin, Camilla

AU - Björk, Johanna K.

AU - Bergman, Heidi A.

AU - Himanen, Samu V.

AU - Kallio, Marko

AU - Roos-Mattjus, Pia

AU - Sistonen, Lea

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AB - 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

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