Dosage‐dependent translational suppression in yeast <i>Saccharomyces cerevisiae</i>

Chernoff, Yury O.; Инге-Вечтомов, С. Г.; Derkach, Irina L.; Ptyushkina, Marina V.; Tarunina, Olga V.; Dagkesamanskaya, Adilya; Ter‐Avanesyan, Michael D.

doi:10.1002/yea.320080702

Cited by 54 publications

(28 citation statements)

References 25 publications

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“…Possibly, increased Sup35 aggregation contributes to cell toxicity. Such an effect of Hsp104-A503V would be similar to consequences of Sup35 (or Sup35N/ NM) overproduction in the [PSI ϩ ] background, which results in both the appearance of large detectable Sup35 clumps (47) and cell toxicity (43,46,48). Therefore, it appears that Hsp104-A503V exhibits opposite effects on the Q103 and Sup35 aggregates, decreasing aggregate size and toxicity in the former case and increasing them in the latter case.…”

Section: Effects Of the Yeast Prionmentioning

confidence: 98%

Modulation of Prion-dependent Polyglutamine Aggregation and Toxicity by Chaperone Proteins in the Yeast Model

Gokhale

Newnam

Sherman

et al. 2005

Journal of Biological Chemistry

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126

107

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In yeast, aggregation and toxicity of the expanded polyglutamine fragment of human huntingtin strictly depend on the presence of the endogenous self-perpetuating aggregated proteins (prions), which contain glutamine/asparagine-rich domains. Some chaperones of the Hsp100/70/40 complex, modulating propagation of yeast prions, were also reported to influence polyglutamine aggregation in yeast, but it was not clear whether they do it directly or via affecting prions. Our data show that although some chaperone alterations indeed act on polyglutamines via curing endogenous prions, other alterations decrease size and ameliorate toxicity of polyglutamine aggregates without affecting prion propagation. Therefore, the role of yeast chaperones in polyglutamine aggregation and toxicity is not restricted only to their effects on the endogenous prions. Moreover, chaperone interactions with prion and polyglutamine aggregates appear to be of a highly specific nature. One and the same chaperone alteration, substitution A503V in the middle region of the chaperone Hsp104, exhibited opposite effects on one of the endogenous prions ([PSI ؉ ], the prion form of Sup35) and on polyglutamines, increasing aggregate size and toxicity in the former case and decreasing them in the latter case. On the other hand, different members of a single chaperone family exhibited opposite effects on one and the same type of aggregates: excess of the Hsp40 chaperone Ydj1 increased polyglutamine aggregate size and toxicity, whereas excess of the other Hsp40 chaperone, Sis1, decreased them. As many stress-defense proteins are conserved between yeast and mammals, these data shed light on possible mechanisms modulating polyglutamine aggregation and toxicity in mammalian cells. Expansion of glutamine repeats (poly-Q)1 in certain proteins is responsible for neurodegenerative disorders. The hallmark of poly-Q diseases is the formation of insoluble cytosolic and nuclear inclusions (1). Huntington disease is one of the best known poly-Q disorders (2). It is caused by an expansion of the poly-Q stretch in the essential protein called huntingtin (Htt) to more than 37 amino acids. The length of the poly-Q stretch inversely correlates with the time of onset of the disease and the time of formation of Htt aggregates (3). The role of various types of aggregates in cell toxicity remains a matter of debate (4). Recent models propose that toxicity of poly-Q Htt arises from sequestration of certain essential proteins by Htt aggregates (5-7). The poly-Q stretch is located within the N-terminal (exon 1) region of Htt, which is involved in numerous proteinprotein interactions (8). The N-terminal fragment of Htt with poly-Q extensions, when expressed in mice, aggregated and was sufficient to cause Huntington disease-like neurodegeneration (9, 10). This indicates that at least some parameters of poly-Q associated aggregation and toxicity could be reproduced in the experimental assays using only N-terminal poly-Q expanded fragments of Htt.Several models for studying poly-Q aggr...

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Section: Effects Of the Yeast Prionmentioning

confidence: 98%

Modulation of Prion-dependent Polyglutamine Aggregation and Toxicity by Chaperone Proteins in the Yeast Model

Gokhale

Newnam

Sherman

et al. 2005

Journal of Biological Chemistry

Self Cite

126

107

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“…In yeast, the presence of the [URE3] prion, or a combination of the [PSI + ] prion with the tRNA suppressor SUQ5 (Eaglestone et al 1999;Jung et al 2000;Schwimmer and Masison 2002), can induce the stress response. Overproduction of Sup35 or its PrD is toxic to [PSI + ] strains (Chernoff et al 1992) and at high levels to [PIN + ] strains, in which de novo [PSI + ] induction is efficient (Derkatch et al 1997), but not to strains lacking any prions. Likewise, Rnq1 overproduction is toxic to [PIN + ] strains (Douglas et al 2008).…”

Section: Biological Effects Of Prionsmentioning

confidence: 99%

Prions in Yeast

2012

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The concept of a prion as an infectious self-propagating protein isoform was initially proposed to explain certain mammalian diseases. It is now clear that yeast also has heritable elements transmitted via protein. Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-b aggregates (amyloids). Recently, there has been an explosion in the number of recognized prions in yeast. Yeast continues to lead the way in understanding cellular control of prion propagation, prion structure, mechanisms of de novo prion formation, specificity of prion transmission, and the biological roles of prions. This review summarizes what has been learned from yeast prions.

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“…Two Sup45p binding sites were localized within Sup35p, one at the NM border and another in the first half of C (34) (38,45,46). Possibly the unbalanced excess of one of the release factors allows it to deplete the termination complex of an essential protein.…”

Section: Sup35p Is An Erf3 Translational Termination Factormentioning

confidence: 99%

The Yeast [PSI+] Prion: Making Sense of Nonsense

Liebman

Derkatch

1999

Journal of Biological Chemistry

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] was shown to be an "omnipotent" suppressor because it could cause readthrough of certain UAA, UAG, and UGA codons in the absence of other suppressors or drugs (11). Similar allosuppressor and omnipotent suppressor phenotypes were also associated with different sup35 and sup45 mutant alleles. However, whereas the sup35 and sup45 mutations were recessive and showed the 2:2 segregation pattern expected of Mendelian genes, the [PSI

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Dosage‐dependent translational suppression in yeast Saccharomyces cerevisiae

Cited by 54 publications

References 25 publications

Modulation of Prion-dependent Polyglutamine Aggregation and Toxicity by Chaperone Proteins in the Yeast Model

Modulation of Prion-dependent Polyglutamine Aggregation and Toxicity by Chaperone Proteins in the Yeast Model

Prions in Yeast

The Yeast [PSI+] Prion: Making Sense of Nonsense

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