title: Circumvention of chaperone requirement for aggregate formation of a short polyglutamine tract by the co-expression of a long polyglutamine tract.
abstract: Polyglutamine disease is now recognized as one of the conformational, amyloid-related diseases. In this disease, polyglutamine expansion in proteins has toxic effects on cells and also results in the formation of aggregates. Polyglutamine aggregate formation is accompanied by conversion of the polyglutamine from a soluble to an insoluble form. In yeast, the efficiency of the aggregate formation is determined by the balance of various parameters, including the length of the polyglutamine tract, the function of Hsp104, and the level of polyglutamine expression. In this study, we found that the co-expression of a long polyglutamine tract, which formed aggregates independently of the function of Hsp104, enhanced the formation of aggregates of a short polyglutamine tract in wild-type cells as well as in Deltahsp104 mutant cells. Thus, the expression of a long polyglutamine tract would be an additional parameter determining the efficiency of aggregate formation of a short polyglutamine tract. The co-localization of aggregates of long and short polyglutamine tracts suggests the possibility that the enhancement occurs due to the seeding of aggregates of the long polyglutamine tracts.
authors.affiliation: Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo, Tokyo 113-8613, Japan. ykimura@rinshoken.or.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Sumiko
authors.initials: S
authors.lastname: Koitabashi
authors.forename: Akira
authors.initials: A
authors.lastname: Kakizuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000235:genetics; D001483:Base Sequence; D052160:Benzothiazoles; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005822:Genetic Vectors; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010957:Plasmids; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles
chemical_list: D052160:Benzothiazoles; D005456:Fluorescent Dyes; D018832:Molecular Chaperones; D016328:NF-kappa B; D010455:Peptides; D011089:Polydeoxyribonucleotides; D011994:Recombinant Proteins; D013844:Thiazoles; C009462:thioflavin T; C097188:polyglutamine