Activation of heat shock genes is not necessary for protection by heat shock transcription factor 1 against cell death due to a single exposure to high temperatures.
Heat shock response, which is characterized by the induction of a set of heat shock proteins, is essential for induced thermotolerance and is regulated by heat shock transcription factors (HSFs). Curiously, HSF1 is essential for heat shock response in mammals, whereas in avian HSF3, an avian-specific factor is required for the burst activation of heat shock genes. Amino acid sequences of chicken HSF1 are highly conserved with human HSF1, but those of HSF3 diverge significantly. Here, we demonstrated that chicken HSF1 lost the ability to activate heat shock genes through the amino-terminal domain containing an alanine-rich sequence and a DNA-binding domain. Surprisingly, chicken and human HSF1 but not HSF3 possess a novel function that protects against a single exposure to mild heat shock, which is not mediated through the activation of heat shock genes. Overexpression of HSF1 mutants that could not bind to DNA did not restore the susceptibility to cell death in HSF1-null cells, suggesting that the new protective role of HSF1 is mediated through regulation of unknown target genes other than heat shock genes. These results uncover a novel role of vertebrate HSF1, which has been masked under the roles of heat shock proteins.
Inouye
Sachiye
S
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
Katsuki
Kensaku
K
Izu
Hanae
H
Fujimoto
Mitsuaki
M
Sugahara
Kazuma
K
Yamada
Shu-Ichi
S
Shinkai
Yoichi
Y
Oka
Yoshitomo
Y
Katoh
Yumiko
Y
Nakai
Akira
A
D000256:Adenoviridae / Q000235:genetics; D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D015152:Blotting, Northern; D016923:Cell Death; D002460:Cell Line; D002645:Chickens; D002850:Chromatography, Gel; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D017353:Gene Deletion; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions; D013696:Temperature; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors
D030161:Avian Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; C095720:HSF3 protein, Gallus gallus; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D000409:Alanine