A novel mouse HSF3 has the potential to activate nonclassical heat-shock genes during heat shock.
The heat-shock response is characterized by the expression of a set of classical heat-shock genes, and is regulated by heat-shock transcription factor 1 (HSF1) in mammals. However, comprehensive analyses of gene expression have revealed very large numbers of inducible genes in cells exposed to heat shock. It is believed that HSF1 is required for the heat-inducible expression of these genes although HSF2 and HSF4 modulate some of the gene expression. Here, we identified a novel mouse HSF3 (mHSF3) translocated into the nucleus during heat shock. However, mHSF3 did not activate classical heat-shock genes such as Hsp70. Remarkably, overexpression of mHSF3 restored the expression of nonclassical heat-shock genes such as PDZK3 and PROM2 in HSF1-null mouse embryonic fibroblasts (MEFs). Although down-regulation of mHSF3 expression had no effect on gene expression or cell survival in wild-type MEF cells, it abolished the moderate expression of PDZK3 mRNA and reduced cell survival in HSF1-null MEF cells during heat shock. We propose that mHSF3 represents a unique HSF that has the potential to activate only nonclassical heat-shock genes to protect cells from detrimental stresses.
Department of Biochemistry, Yamaguchi University School of Medicine, Ube, Japan.
Mitsuaki
M
Fujimoto
Naoki
N
Hayashida
Takuma
T
Katoh
Kouji
K
Oshima
Toyohide
T
Shinkawa
Ramachandran
R
Prakasam
Ke
K
Tan
Sachiye
S
Inouye
Ryosuke
R
Takii
Akira
A
Nakai
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D002522:Chlorocebus aethiops; D019610:Cytoprotection; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D013312:Stress, Physiological; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism*
C547873:HSF3 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; C513194:Smarca4 protein, mouse; D004265:DNA Helicases