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Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity

Oncogene volume 28, pages 3332–3344 (2009)Cite this article

Abstract

Heat shock protein 27 (HSP27) accumulates in stressed cells and helps them to survive adverse conditions. We have already shown that HSP27 has a function in the ubiquitination process that is modulated by its oligomerization/phosphorylation status. Here, we show that HSP27 is also involved in protein sumoylation, a ubiquitination-related process. HSP27 increases the number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3 but this effect shows some selectivity as it neither affects all proteins nor concerns SUMO-1. Moreover, no such alteration in SUMO-2/3 conjugation is achievable by another HSP, such as HSP70. Heat shock factor 1 (HSF1), a transcription factor responsible for HSP expression, is one of the targets of HSP27. In stressed cells, HSP27 enters the nucleus and, in the form of large oligomers, binds to HSF1 and induces its modification by SUMO-2/3 on lysine 298. HSP27-induced HSF1 modification by SUMO-2/3 takes place downstream of the transcription factor phosphorylation on S303 and S307 and does not affect its DNA-binding ability. In contrast, this modification blocks HSF1 transactivation capacity. These data show that HSP27 exerts a feedback inhibition of HSF1 transactivation and enlighten the strictly regulated interplay between HSPs and HSF1. As we also show that HSP27 binds to the SUMO-E2-conjugating enzyme, Ubc9, our study raises the possibility that HSP27 may act as a SUMO-E3 ligase specific for SUMO-2/3.

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Acknowledgements

We thank L Sistonen and J Anckar (Turku Centre for Biotechnology, Finland) for HSF1 and SUMO-2/3 tools, their helpful advices and discussions. We thank M Gaestel and A Vertii for sharing with us HSP27 phosphorylation mutants’ constructions. This work was supported by grants from the ‘Ligue Nationale Contre le Cancer’ and its committees in the ‘Nièvre’ and ‘Sâone et Loire’. MB and ALJ are recipients of a doctoral fellowship from the ‘Ligue Nationale contre le Cancer’, ADT has a postdoctoral fellowship from ‘L’Association pour la Recherche contre le Cancer’, and EF has an INCa financing. CG and MP lead teams ‘Labellisées’ from the ‘Ligue Nationale contre le Cancer’.

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Authors and Affiliations

  1. INSERM U866, Dijon, France,

    M Brunet Simioni, A De Thonel, A Hammann, A L Joly, E Fourmaux, A Bouchot & C Garrido

  2. Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, Burgundy, France

    M Brunet Simioni, A De Thonel, A Hammann, A L Joly & C Garrido

  3. Institut de Génétique Moléculaire UMR 5535 CNRS, Montpellier cedex 5, France

    G Bossis & M Piechaczyk

  4. Université Montpellier 2, Montpellier cedex 5, France

    G Bossis & M Piechaczyk

  5. Université Montpellier 1, Montpellier cedex 2, France

    G Bossis & M Piechaczyk

  6. Centre de Recherche en Cancérologie et Département de Médecine, Université Laval, Quebec City, Québec, Canada

    J Landry

  7. CHU Dijon BP1542, Dijon, France

    C Garrido

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  1. M Brunet Simioni
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Correspondence to C Garrido.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Brunet Simioni, M., De Thonel, A., Hammann, A. et al. Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity. Oncogene 28, 3332–3344 (2009). https://doi.org/10.1038/onc.2009.188

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