Hsp105 reduces the protein aggregation and cytotoxicity by expanded-polyglutamine proteins through the induction of Hsp70.
Hsp105alpha and Hsp105beta are major heat shock proteins in mammalian cells and belong to the HSP105/110 family. Hsp105alpha is expressed constitutively in the cytoplasm of cells, while Hsp105beta, an alternatively spliced form of Hsp105alpha, is expressed specifically in the nucleus of cells during mild heat shock. Here, we show that not only Hsp105beta but also Hsp105alpha accumulated in the nucleus of cells following the expression of enhanced green fluorescent protein with a pathological length polyQ tract (EGFP-polyQ97) and suppressed the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. Mutants of Hsp105alpha and Hsp105beta 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 Hsp105alpha and EGFP-polyQ97, and the knockdown of Hsp70 reduced the inhibitory effect of Hsp105alpha and Hsp105beta on the intranuclear aggregation of polyQ proteins and apoptosis induced by EGFP-polyQ97. These observations suggested that Hsp105alpha and Hsp105beta suppressed the expanded polyQ tract-induced protein aggregation and apoptosis through the induction of Hsp70.
Yamagishi
Nobuyuki
N
Department of Biochemistry and Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Goto
Kazumasa
K
Nakagawa
Satomi
S
Saito
Youhei
Y
Hatayama
Takumi
T
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D011232:Chemical Precipitation; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055503:Protein Multimerization / Q000235:genetics; D011506:Proteins / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid / Q000502:physiology
D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C097205:HSPH1 protein, human; D010455:Peptides; D011506:Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C097188:polyglutamine