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J. Biol. Chem., Vol. 277, Issue 40, 37536-37541, October 4, 2002

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Circumvention of Chaperone Requirement for Aggregate Formation of a Short Polyglutamine Tract by the Co-expression of a Long Polyglutamine Tract^*

Yoko Kimura^§, Sumiko Koitabashi, Akira Kakizuka^¶, and Takashi Fujita

From the  Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo, Tokyo 113-8613, Japan and the ^¶ Department of Functional Biology, Kyoto University Graduate School of Biostudies, Yosidakonoe, Sakyo, Kyoto 606-8501, Japan

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 hsp104 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.

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				Y. Kimura, S. Koitabashi, A. Kakizuka, and T. Fujita The role of pre-existing aggregates in Hsp104-dependent polyglutamine aggregate formation and epigenetic change of yeast prions Genes Cells, August 1, 2004; 9(8): 685 - 696. [Abstract] [Full Text] [PDF]