Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1

Carina I. Holmberg, Ville Hietakangas, Andrey Mikhailov, Jouni O. Rantanen, Marko Kallio, Annika Meinander, Jukka Hellman, Nick Morrice, Carol MacKintosh, Richard I. Morimoto, John E. Eriksson, Lea Sistonen*

*Corresponding author for this work

Research output: Contribution to journalArticle

224 Scopus citations

Abstract

Heat shock factor 1 (HSF1) is a serine-rich constitutively phosphorylated mediator of the stress response. Upon stress, HSF1 forms DNA-binding trimers, relocalizes to nuclear granules, undergoes inducible phosphorylation and acquires the properties of a transactivator. HSF1 is phosphorylated on multiple sites, but the sites and their function have remained an enigma. Here, we have analyzed sites of endogenous phosphorylation on human HSF1 and developed a phosphopeptide antibody to identify Set230 as a novel in viva phosphorylation site. Set230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Set230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in viva Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1-/- cells. Our study provides the first evidence that phosphorylation is essential for the transcriptional activity of HSF1, and hence for induction of the heat shock response.

Original languageEnglish (US)
Pages (from-to)3800-3810
Number of pages11
JournalEMBO Journal
Volume20
Issue number14
DOIs
StatePublished - Jul 16 2001

Keywords

  • Heat shock factor 1
  • Heat shock response
  • Phosphorylation
  • Transcription

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1'. Together they form a unique fingerprint.

  • Cite this

    Holmberg, C. I., Hietakangas, V., Mikhailov, A., Rantanen, J. O., Kallio, M., Meinander, A., Hellman, J., Morrice, N., MacKintosh, C., Morimoto, R. I., Eriksson, J. E., & Sistonen, L. (2001). Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO Journal, 20(14), 3800-3810. https://doi.org/10.1093/emboj/20.14.3800