Hsp105 reduces the protein aggregation and cytotoxicity by expanded-polyglutamine proteins through the induction of Hsp70

作者：Yamagishi Nobuyuki; Goto Kazumasa; Nakagawa Satomi; Saito Youhei; Hatayama Takumi^*

来源：Experimental Cell Research, 2010, 316(15): 2424-2433.

DOI：10.1016/j.yexcr.2010.06.003

• Hsp105 alpha
• Hsp105 beta
• Hsp70
• Polyglutamine diseases
• Protein aggregation

Hsp105 alpha and Hsp105 beta are major heat shock proteins in mammalian cells and belong to the HSP105/110 family. Hsp105 alpha is expressed constitutively in the cytoplasm of cells, while Hsp105 beta, an alternatively spliced form of Hsp105 alpha, is expressed specifically in the nucleus of cells during mild heat shock. Here, we show that not only Hsp105 beta but also Hsp105 alpha accumulated in the nucleus of cells following the expression of enhanced green fluorescent protein with a pathological length polyQtract (EGFP-polyQ97) and suppressed the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. Mutants of Hsp105 alpha and Hsp105 beta with changes in the nuclear localization signal sequences, which localized exclusively in the cytoplasm with or without the expression of EGFP-polyQ97, did not suppress the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. Furthermore, Hsp70 was induced by the co-expression of Hsp105 alpha and EGFP-polyQ97, and the knockdown of Hsp70 reduced the inhibitory effect of Hsp105 alpha and Hsp105 beta on the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. These observations suggested that Hsp105 alpha and Hsp105 beta suppressed the expanded polyQ tract-induced protein aggregation and apoptosis through the induction of Hsp70.

• 出版日期2010-9-10