Expression of HSF2 Decreases in Mitosis to Enable Stress-Inducible Transcription and Cell Survival

J Cell Biol. 2014 Sep 15;206(6):735-49. doi: 10.1083/jcb.201402002. Epub 2014 Sep 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Survival
  • Chromatin / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics
  • HeLa Cells
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / biosynthesis
  • Heat-Shock Proteins / genetics*
  • 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 Factors / genetics*
  • Transcription, Genetic

Substances

  • Chromatin
  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • HSF2 protein, human
  • RNA Polymerase II