Heterotrimerization of Heat-Shock Factors 1 and 2 Provides a Transcriptional Switch in Response to Distinct Stimuli

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Sandqvist A, Björk JK, Åkerfelt M, Chitikova Z, Grichine A, Vourch C, Jolly C, Salminen TA, Nymalm Y, Sistonen L
Publisher: AMER SOC CELL BIOLOGY
Publication year: 2009
Journal: Molecular Biology of the Cell
Journal acronym: MOL BIOL CELL
Volume number: 20
Issue number: 5
Start page: 1340
End page: 1347
Number of pages: 8
ISSN: 1059-1524
eISSN: 1939-4586


Abstract

Organisms respond to circumstances threatening the cellular protein homeostasis by activation of heat-shock transcription factors (HSFs), which play important roles in stress resistance, development, and longevity. Of the four HSFs in vertebrates (HSF1-4), HSF1 is activated by stress, whereas HSF2 lacks intrinsic stress responsiveness. The mechanism by which HSF2 is recruited to stress-inducible promoters and how HSF2 is activated is not known. However, changes in the HSF2 expression occur, coinciding with the functions of HSF2 in development. Here, we demonstrate that HSF1 and HSF2 form heterotrimers when bound to satellite III DNA in nuclear stress bodies, subnuclear structures in which HSF1 induces transcription. By depleting HSF2, we show that HSF1-HSF2 heterotrimerization is a mechanism regulating transcription. Upon stress, HSF2 DNA binding is HSF1 dependent. Intriguingly, when the elevated expression of HSF2 during development is mimicked, HSF2 binds to DNA and becomes transcriptionally competent. HSF2 activation leads to activation of also HSF1, revealing a functional interdependency that is mediated through the conserved trimerization domains of these factors. We propose that heterotrimerization of HSF1 and HSF2 integrates transcriptional activation in response to distinct stress and developmental stimuli.

Last updated on 2019-19-08 at 06:36

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