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

Alexandra Elsing, Camilla Aspelin, Johanna Björk, Heidi Bergman, Samu Himanen, Marko Kallio, Pia Roos-Mattjus, Lea Sistonen

    Research output: Contribution to journalArticleScientificpeer-review

    22 Citations (Scopus)

    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 languageUndefined/Unknown
    Pages (from-to)735–749
    Number of pages15
    JournalJournal of Cell Biology
    Volume206
    Issue number6
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

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