Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance

Masako Tanabe, Yoshinori Kawazoe, Shunichi Takeda, Richard I. Morimoto, Kazuhiro Nagata, Akira Nakai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

The vertebrate genome encodes a family of heat shock factors (HSFs 1-4) of which the DNA-binding and transcriptional activities of HSF1 and HSF3 are activated upon heat shock. HSF1 has the properties of a classical HSF and exhibits rapid activation of DNA-binding and transcriptional activity upon exposure to conditions of heat shock and other stresses, whereas HSF3 typically is activated at higher temperatures and with distinct delayed kinetics. To address the role of HSF3 in the heat shock response, null cells lacking the HSF3 gene were constructed by disruption of the resident gene by somatic recombination in an avian lymphoid cell line. Null cells lacking HSF3, yet expressing normal levels of HSF1, exhibited a severe reduction in the heat shock response, as measured by inducible expression of heat shock genes, and did not exhibit thermotolerance. At intermediate heat shock temperatures, where HSF1 oligomerizes to an active trimer in wild-type cells, HSF1 remained as an inert monomer in the HSF3 null cell line. HSF3 null cells were restored to a nearly normal heat shock-responsive state by reintroduction of an exogenous HSF3 gene. These results reveal that HSF3 has a dominant role in the regulation of the heat shock response and directly influences HSF1 activity.

Original languageEnglish (US)
Pages (from-to)1750-1758
Number of pages9
JournalEMBO Journal
Volume17
Issue number6
DOIs
StatePublished - Mar 16 1998

Keywords

  • HSF
  • Heat shock
  • Stress response
  • Thermotolerance
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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