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

• Published in: Oncogene Vol. 28; no. 37; pp. 3332 - 3344
• Main Authors: Brunet Simioni, M, De Thonel, A, Hammann, A, Joly, A L, Bossis, G, Fourmaux, E, Bouchot, A, Landry, J, Piechaczyk, M, Garrido, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-09-2009; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Animals; Apoptosis; Biochemistry, Molecular Biology; Biological and medical sciences; Cancer; Cell Biology; Cell Nucleus - metabolism; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; DNA-Binding Proteins - metabolism; Enzymes; Feedback inhibition; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetics; Heat shock factors; Heat shock proteins; Heat Shock Transcription Factors; HeLa Cells; HSF1 protein; HSP27 Heat-Shock Proteins - chemistry; HSP27 Heat-Shock Proteins - metabolism; Hsp27 protein; Hsp70 protein; Human Genetics; Humans; Internal Medicine; Life Sciences; Lysine; Medicine; Medicine & Public Health; Molecular and cellular biology; Molecular genetics; Oligomerization; Oncology; original-article; Phosphorylation; Physiological aspects; Protein Multimerization; Protein Structure, Quaternary; Protein Transport; Small Ubiquitin-Related Modifier Proteins - metabolism; Substrate Specificity; SUMO protein; Transcription factors; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Ubiquitin; Ubiquitin-proteasome system; Ubiquitin-protein ligase; Ubiquitination; Ubiquitins - metabolism; France; stress; cancer; transcriptional activity; SUMOylation; HSP27; HSF1; Transcription; Heat shock protein; Sumoylation; Malignant tumor; Transcription factor; Carcinogenesis; Stress; Cancer; 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
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2009.188

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.