Hsp105[beta] upregulates hsp70 gene expression through signal transducer and activator of transcription-3

• Published in: The FEBS journal 2009-10, Vol.276 (20), p.5870
• Main Authors: Yamagishi, Nobuyuki, Fujii, Hajime, Saito, Youhei, Hatayama, Takumi
• Format: Article
• Language: English
• Subjects: Amino acids; Biochemistry; Cellular biology; Oxidation; Proteins
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2009.07311.x

Hsp105α and Hsp105[beta] are mammalian members of the Hsp105/110 family, a divergent subgroup of the Hsp70 family. Hsp105α is expressed constitutively and induced by various forms of stress, whereas Hsp105[beta] is an alternatively spliced form of Hsp105α that is expressed specifically during mild heat shock. In a report, it was shown that Hsp105α and Hsp105[beta] localize to the cytoplasm and of nucleus of cells, respectively, and that Hsp105[beta], but not Hsp105α, induces the expression of Hsp70 in mammalian cells. Here, we examined the mechanism by which Hsp105[beta] induces the expression of Hsp70. Using a series of deletion mutants of Hsp105[beta], it was revealed that the region between amino acids 642 and 662 of Hsp105[beta] is necessary for the activation of the hsp70 promoter by Hsp105[beta]. 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 Hsp105[beta]. In addition, overexpression of Hsp105[beta] 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 Hsp105[beta]. Furthermore, downregulation of Hsp105[beta] reduced the expression of Hsp70 in heat-shocked cells. On the basis of these findings, it is suggested that Hsp105[beta] induces Hsp70 expression markedly through the STAT3 pathway in heat-shocked cells. This may represent the mechanism that connects the heat shock protein and STAT families for cell defense against deleterious stress. [PUBLICATION ABSTRACT]