Skip to main content
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;7(4):425–435. doi: 10.1111/j.1582-4934.2003.tb00245.x

Phenotypic characterization of mouse embryonic fibroblasts lacking heat shock factor 2

Liliana Paslaru 1,, M Morange 2, Valérie Mezger 2
PMCID: PMC6740138  PMID: 14754511

Abstract

In murine cells, the heat shock response is regulated by a transcription factor, HSF1, which triggers the transcription of heat shock genes. HSF2 has been shown to be involved in meiosis and mouse brain development. We characterized the effects of the absence of HSF2 in mouse embryonic fibroblasts (MEFs). The temperature threshold of the heat shock response appeared lowered in Hsf2 ‐/‐ MEFS as monitored by the synthesis of heat shock protein HSP70. In contrast to unstressed wild type MEFS, HSP70 and HSF1 are localized in the nucleus of unstressed Hsf2 ‐/‐ MEFS, a characteristic of stressed cells. HSF1 is not activated for DNA‐binding at unstressed temperature in Hsf2 ‐/‐ MEFS. Therefore, the absence of HSF2 induces some but not all of the characteristics of the stress response. In addition, Hsf2 ‐/‐ MEFS exhibited proliferation defects, altered morphology, remodeling of the fibronectin network.

Keywords: Heat shock response, heat shock transcription factors, HSF1, HSF2, mouse embryonic fibroblasts, proliferation

References

  • 1. Pirkalla L., Nykänen P., Sistonen L. Roles of the heat shock transcripion factors in the regulation of the heat shock response and beyond. FASEB J. 15: 1118–1131, 2001. [DOI] [PubMed] [Google Scholar]
  • 2. Xiao X., Zuo X., Davis A.A., McMillan D.R., Curry B.B., Richadson J.A., Benjamin I.J. HSF1 is required for extra‐embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J. 18: 5943–5952, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Christians E., Davis A.A., Thomas S.D., Benjamin I.J. Maternal effect of Hsf1 in reproductive success. Nature. 407: 693–694, 2000. [DOI] [PubMed] [Google Scholar]
  • 4. Kallio M., Chang Y., Manuel M., Alastalo T.‐P., Rallu M., Gitton Y., Pirkkala L., Loones M.‐T., Paslaru L., Larney S., Hiard S., Morange M., Sistonen L., Mezger V. Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice. EMBO J., 21: 2591–2601, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Wang G., Zhang J., Moskophidis D., Mivechi N.F.. Targeted disruption of the heat shock transcription factor (hsf)‐2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis. Genesis. 36: 48–61, 2003. [DOI] [PubMed] [Google Scholar]
  • 6. Sarge K.D., Zimarino V., Holm K., Wu C., Morimoto, R.I. , Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA‐binding ability, Genes Dev. 5: 1902–1911, 1991. [DOI] [PubMed] [Google Scholar]
  • 7. Sheldon L. A., Kingston R. E. Hydrophobic coiled‐coil domains regulate the subcellular localization of human heat shock factor 2. Genes Dev. 7: 1549–1558, 1993. [DOI] [PubMed] [Google Scholar]
  • 8. Mathew A., Mathur S. K., Jolly C., Fox S.G., Kim S., Morimoto, R. I. . Stress‐specific activation and repression of heat shock factors1 and 2. Mol. Cell. Biol. 21: 7163–7171, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. He H, Soncin F, Grammatikakis N, Li Y, Siganou A, Gong J, Brown SA, Kingston RE, Calderwood SK. Elevated expression of heat shock factor (HSF) 2A stimulates HSF1‐induced transcription during stress. J. Biol. Chem., 278: 35465–35475, 2003. [DOI] [PubMed] [Google Scholar]
  • 10. Alastalo TP, Hellesuo M, Sandqvist A, Hietakangas V, Kallio M, Sistonen L. Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp 70. J. Cell. Sci., 116: 3557–3570, 2003. [DOI] [PubMed] [Google Scholar]
  • 11. Jolly C., Usson Y., Morimoto R.I. Rapid and reversible relocalization of heat shock factor 1 within seconds to nuclear stress granules. Proc. Natl. Acad. Sci. USA, 96: 6769–6774, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227: 680–685, 1970. [DOI] [PubMed] [Google Scholar]
  • 13. Paslaru L., Rallu M., Manuel M., Davidson S., Morange M. Cyclosporine A induces an Atypical heat shock response. Biochem. Biophys. Res. Commun., 269: 464–469, 2000. [DOI] [PubMed] [Google Scholar]
  • 14. Bruce J.L., Chen C., Xie Y., Zhong R., Wang Y., Stevenson M.A., Calderwood S.K. Activation of heat shock transcription factor 1 to a DNA binding form during the G1 phase of the cell cycle. Cell Stress Chaperones. 4: 36–45, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Welch W. J., Feramisco J. R. Nuclear and nucleolar localization of the 72,000‐dalton heat shock protein in heat‐shocked mammalian cells. J. Biol. Chem., 259: 4501–4513, 1984. [PubMed] [Google Scholar]
  • 16. Welch W. J., Suhan, J. P. , Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J. Cell Biol., 103: 2035–2052, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Morimoto R.I. Dynamic remodeling of transcription complex by molecular chaperones. Cell, 110: 281–284, 2002. [DOI] [PubMed] [Google Scholar]
  • 18. Davidson SM, Morange M. Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes. Dev Biol., 218: 146–160, 2000. [DOI] [PubMed] [Google Scholar]
  • 19. Duverger O., Paslaru L., Morange M. HSP25 is involved in two steps of the differentiation of PAM212 keratynocytes. J. Biol. Chem. Revised manuscript. [DOI] [PubMed]
  • 20. Colombi M., Zoppi N., De Petro G., Marchina E., Gardella R., Tavian D., Ferraboli S., Barlati Dagger S.. Matrix assembly induction and cell migration and invasion inhibition by a 13‐amino acid fibronectin peptide. J. Biol. Chem., 278: 14346–14355, 2003. [DOI] [PubMed] [Google Scholar]
  • 21. Christians E., Michel E., Adenot P., Mezger V., Rallu M., Morange M., Renard J.P. Evidence for the involvement of mouse heat shock factor 1 in the atypical expression of the HSP70.1 heat shock gene during mouse zygotic genome activation. Mol. Cell. Biol. 17: 778–788, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES