Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70.
The heat-shock response is characterized by the activation of heat-shock transcription factor 1 (HSF1), followed by increased expression of heat-shock proteins (Hsps). The stress-induced subnuclear compartmentalization of HSF1 into nuclear stress granules has been suggested to be an important control step in the regulation of stress response and cellular homeostasis in human cells. In this study, we demonstrate that the less-well characterized HSF2 interacts physically with HSF1 and is a novel stress-responsive component of the stress granules. Based on analysis of our deletion mutants, HSF2 influences to the localization of HSF1 in stress granules. Moreover, our results indicate that the stress granules are dynamic structures and suggest that they might be regulated in an Hsp70-dependent manner. The reversible localization of Hsp70 in the nucleoli strictly coincides with the presence of HSF1 in stress granules and is dramatically suppressed in thermotolerant cells. We propose that the regulated subcellular distribution of Hsp70 is an important regulatory mechanism of HSF1-mediated heat shock response.
Alastalo
Tero-Pekka
TP
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, BioCity, PO Box 123, FIN-20521 Turku, Finland.
Hellesuo
Maria
M
Sandqvist
Anton
A
Hietakangas
Ville
V
Kallio
Marko
M
Sistonen
Lea
L
D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human