Prions Affect the Appearance of Other Prions

Derkatch, Irina L.; Bradley, Michael E.; Hong, Joo Y.; Liebman, Susan W.

doi:10.1016/s0092-8674(01)00427-5

Cited by 550 publications

(675 citation statements)

References 53 publications

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“…This observation stimulated the first sequence-based query for additional yeast prions (Sondheimer and Lindquist 2000) that ultimately lead to the identification of an additional prion protein called Rnq1. The prion form of Rnq1, [RNQ+], was found to underlie the previously characterized non-Mendelian trait [PIN+], which facilitates the de novo appearance of [URE3] and [PSI+] (Derkatch et al 2000;Derkatch et al 2001). Rnq1, however, not only induces benign conformational transitions of other prion proteins, it can also induce toxic conformational changes of glutamine-expansion (polyQ) proteins that cause Huntington's disease and several other late-onset neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

Alberti

Halfmann

Lindquist

2010

Methods in Enzymology

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Section: Introductionmentioning

confidence: 99%

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

Alberti

Halfmann

Lindquist

2010

Methods in Enzymology

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“…The yeast prion [RNQ ϩ ] is determined by the conformational state of the Rnq1 protein, which contains a C-terminal asparagineand glutamine-rich prion domain and an N-terminal non-prionforming domain (14,15 (19,20). [RNQ ϩ ] prions also cause the exon 1 fragment of huntingtin protein, containing glutamine repeats, to become toxic in yeast (16).…”

mentioning

confidence: 99%

Chaperone-dependent amyloid assembly protects cells from prion toxicity

Douglas

Treusch

Ren³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

161

234

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amyloid formation exacerbated Rnq1 toxicity. These and other data establish that even subtle changes in the folding homeostasis of an amyloidogenic protein can create a severe proteotoxic gain-of-function phenotype and that chaperone-mediated amyloid assembly can be cytoprotective. The possible relevance of these findings to other phenomena, including prion-driven neurodegenerative diseases and heterokaryon incompatibility in fungi, is discussed.Hsp40 ͉ neurodegenerative disease ͉ Sis1 ͉ Rnq1 ͉ yeast prion

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“…Alternatively, we can not exclude the possibility that the seeding may not be the only mechanism to enhance p50-Q34 aggregate formation by the expression of 3HA-Q80. There may be inhibitory factors for aggregate formation for p50-Q34, whose inhibitory activity is suppressed by the expression of 3HA-Q80, as has been proposed based on yeast prion studies (18,19).…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, prion-like factors with glutamine/asparagine-rich domains were reported to enhance the aggregation of different prion-like factors and of polyglutamine tracts (18,19). These results led us to ask if co-expression of a long polyglutamine tract, which is rather Hsp104-independent for aggregate formation, could circumvent the chaperone requirement for polygluatmine aggregate formation of a short polyglutamine tract.…”

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confidence: 99%

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

Kimura

Koitabashi

Kakizuka

et al. 2002

Journal of Biological Chemistry

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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.Expansion of polyglutamine repeats in a protein has now been proved to account for the pathogenesis of at least nine inherited neurodegenerative diseases, including spinobulbar muscular atrophy, Huntington's disease, spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17 (SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and SCA17, respectively), and dentatorubural pallidoluysian atrophy (1-4). The expression of polyglutamine repeats is sufficient to cause neurodegeneration or toxicity in model organisms and cell death in cultured cells (5-11). The clinical severity and the age of onset of disease symptoms are mainly determined by the length of the polyglutamine in the protein responsible, that is, the longer the polyglutamine, the earlier the onset, and the more severe the disease. Moreover, the deposition of aggregates that contain the expanded polyglutamine is a hallmark of the affected organs and dying cells, and the ability of the expanded polyglutamine to induce these toxic phenomena appears to be inseparably linked with its ability to form aggregates. Thus, the conformational change of the expanded polyglutamine is likely a pathogenic mechanism causing these diseases, although whether the aggregates themselves are pathogenic or not is unknown. Moreover, staining of the brain of Huntington's disease patients with Congo Red suggests that polyglutamine diseases are associated with amyloid fibrils (12).Polyglutamine aggregate formation of amyloid-like appearance has been observed in vitro (13-15). These studies indicate that aggregate formation is autonomous in vitro in the length-, concentration-, and time-dependent manner of a polyglutamine. However, in vivo, in yeast, polyglutamine aggregate formation requires the function of the molecular chaperone Hsp104, a member of the AAA ϩ superfamily, in addition to the parameters noted above (16,17). Upon induction of...

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Prions Affect the Appearance of Other Prions

Cited by 550 publications

References 53 publications

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast

Chaperone-dependent amyloid assembly protects cells from prion toxicity

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

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