Heat shock protein hsp70 accelerates the recovery of heat-shocked mammalian cells through its modulation of heat shock transcription factor HSF1.
The role of mammalian 70-kDa heat shock protein (hsp70) in regulating cellular response to heat shock was examined by using three closely related rat cells: control Rat-1 cells, thermotolerant Rat-1 (TT Rat-1) cells, and heat-resistant M21 cells, a derivative of Rat-1 cells that constitutively overexpress human hsp70. In all these cells, after a prescribed heat shock, the level of the phosphorylated form of heat shock transcription factor HSF1 and that of HSF1 capable of binding to its cognitive DNA sequence heat shock element (HSE) exhibit similar time dependence. The amount of a constitutive HSE-binding activity (CHBA), on the other hand, inversely correlates with those of the two aforementioned forms of HSF1. The recovery kinetics from heat shock are different for the three cell lines, with the thermal-resistant TT Rat-1 and M21 cells showing faster recovery in terms of the state of phosphorylation of HSF1 and its ability to bind HSE or in terms of the reappearance of CHBA. Treatment with okadaic acid, a serine/threonine phosphatase inhibitor, delays the recovery kinetics of Rat-1 cells but not that of thermal-resistant M21 cells. These results are interpreted in terms of a role for hsp70 in the recovery of heat-shocked mammalian cells.
Kim
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Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Ouyang
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H
Li
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GC
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000494:pharmacology; D005347:Fibroblasts; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D009838:Oligodeoxyribonucleotides; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014157:Transcription Factors; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases