Cell cycle transition under stress conditions controlled by vertebrate heat shock factors.
The roles of heat shock transcription factors (HSFs) under physiological conditions have recently become the focus of intense study. We generated avian cells lacking two heat-inducible HSFs, HSF1 and HSF3. In addition to complete loss of activation of heat shock genes under stress conditions, these cells exhibited a marked reduction in Hsp90alpha expression under normal growth conditions. Reduction in Hsp90alpha expression caused instability of a cyclin-dependent kinase, Cdc2, and cell cycle progression was blocked mainly at the G2 phase, but also at G1 phase even at mild heat shock temperatures. Restoration of Hsp90alpha expression rescued the temperature sensitivity without induction of HSPS: We demonstrated for the first time a molecular target affected by heat shock in vivo that causes cell cycle arrest in vertebrates and a novel mechanism of stress resistance controlled by vertebrate HSFS:
Nakai
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Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 775-8505, Japan. anakai@po.cc.yamaguchi-u.ac.jp
Ishikawa
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D000818:Animals; D030161:Avian Proteins; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D002645:Chickens; D003001:Cloning, Molecular; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014714:Vertebrates
D030161:Avian Proteins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; C095720:HSF3 protein, Gallus gallus; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C070389:HSF2 protein, human; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases