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

M. Brunet Simioni , A. de Thonel , A. Hammann , A. L. Joly , G. Bossis (1) , E. Fourmaux , A. Bouchot , J. Landry , Marc Piechaczyk , C. Garrido

1 IGMM - Institut de Génétique Moléculaire de Montpellier

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.

Mots clés: Animals Cell Nucleus/metabolism DNA-Binding Proteins/*metabolism HSP27 Heat-Shock Proteins/chemistry/*metabolism Hela Cells Humans Protein Multimerization Protein Structure; Quaternary Protein Transport Small Ubiquitin-Related Modifier Proteins/*metabolism Substrate Specificity Transcription Factors/*metabolism Transcriptional Activation Ubiquitins/*metabolism

Domaines: Biochimie, Biologie Moléculaire

M. Brunet Simioni, A. de Thonel, A. Hammann, A. L. Joly, G. Bossis, 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, 2009, 28 (37), pp.3332--44. ⟨10.1038/onc.2009.188⟩. ⟨hal-02194091⟩