TAILIEUCHUNG - Báo cáo khoa học: Hsp105b upregulates hsp70 gene expression through signal transducer and activator of transcription-3

Hsp105aand Hsp105bare mammalian members of the Hsp105⁄110 family, a divergent subgroup of the Hsp70 family. Hsp105ais expressed constitu-tively and induced by various forms of stress, whereas Hsp105bis an alter-natively spliced form of Hsp105athat is expressed specifically during mild heat shock. | Hsp105b upregulates hsp70 gene expression through signal transducer and activator of transcription-3 Nobuyuki Yamagishi Hajime Fujii Youhei Saito and Takumi Hatayama Department of Biochemistry Molecular Biology Division of BiologicalSciences Kyoto PharmaceuticalUniversity Japan Keywords heat shock protein Hsp70 Hsp105P nuclear localization STAT3 Correspondence T. Hatayama Department of Biochemistry Molecular Biology Division of Biological Sciences Kyoto PharmaceuticalUniversity 5 Nakauchi-cho Misasagi Yamashina-ku Kyoto 607-8414 Japan Fax 81 75 595 4758 Tel 81 75 595 4653 E-mail hatayama@ Received 14 May 2009 revised 3 August 2009 accepted 7 August 2009 doi Hsp105a and Hsp105b are mammalian members of the Hsp105 110 family a divergent subgroup of the Hsp70 family. Hsp105a is expressed constitutively and induced by various forms of stress whereas Hsp105b is an alternatively spliced form of Hsp105a that is expressed specifically during mild heat shock. In a report it was shown that Hsp105a and Hsp105b localize to the cytoplasm and of nucleus of cells respectively and that Hsp105b but not Hsp105a induces the expression of Hsp70 in mammalian cells. Here we examined the mechanism by which Hsp105b induces the expression of Hsp70. Using a series of deletion mutants of Hsp105b it was revealed that the region between amino acids 642 and 662 of Hsp105b is necessary for the activation of the hsp70 promoter by Hsp105p. Furthermore it was shown that signal transducer and activator of transcription STAT -3 bound to the sequence of the hsp70 promoter between -206 and -187 bp and that mutations of this sequence abrogated the activation of the hsp70 promoter by Hsp105p. In addition overexpression of Hsp105b stimulated the phosphorylation of STAT3 at Tyr705 and its translocation to the nucleus. Downregulation of STAT3 expression resulted in reduction of the activation of the hsp70 promoter by Hsp105p. Furthermore downregulation of .

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• Hsp105aand Hsp105bare mammalian members of the Hsp105⁄110 family
• a divergent subgroup of the Hsp70 family
• Hsp105ais expressed constitu tively and induced by various forms of stress
• whereas Hsp105bis an alter natively spliced form of Hsp105athat is expressed specifically during mild heat shock
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