[URE3] Prion Propagation in <i>Saccharomyces cerevisiae</i>: Requirement for Chaperone Hsp104 and Curing by Overexpressed Chaperone Ydj1p

Moriyama, Hiromitsu; Edskes, Herman K.; Wickner, Reed B.

doi:10.1128/mcb.20.23.8916-8922.2000

Cited by 259 publications

(275 citation statements)

References 58 publications

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“…Overexpression of Ydj1-Hsp40 or Ssa1-Hsp70 (but not Ssa2-Hsp70) is able to cure [URE3] [78,89]. In addition, a missense mutation within the Ssa2-Hsp70 peptide-binding domain alters [URE3] stability [90].…”

Section: Chaperonesmentioning

confidence: 99%

“…Genetic studies have identified a number of chaperones that modulate the behaviour of yeast prions [76]. In particular, the three best characterized S. cerevisiae prions, Sup35, Ure2 and Rnq1, all require normal expression levels of the chaperone Hsp104 in order to be propagated efficiently [13,77,78]. In the case of Sup35, inhibition of the ATPase activity of Hsp104 similarly interferes with prion propagation [79][80][81] and overexpression of Hsp104 also results in curing of the prion phenotype [77].…”

Section: Chaperonesmentioning

confidence: 99%

“…Detailed genetic analysis has identified mutations in both the ATPase and peptide-binding domains of Ssa1-Hsp70 that alter stability of the [PSI + ] prion [91,92]. However, the clear predominance of Hsp70 ATPase domain mutations that alter [PSI + ] propagation suggests that modifying the rate of ATP hydrolysis is a major factor in the ability of Hsp70 to alter prion propagation [92] [78], even though propagation of both prions is dependent on the presence of normal levels of Hsp104. These varying effects most likely reflect differences in amyloid structure of different prions or prion strains and/or subtle differences in substrate preference for related chaperone machineries.…”

Section: Chaperonesmentioning

confidence: 99%

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The yeast prion protein Ure2: Structure, function and folding

Lian

Jiang

Zhang

et al. 2006

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen metabolism and as a glutathione-dependent peroxidase. Ure2 also has the characteristics of a prion, in that it can undergo a heritable conformational change to an aggregated state; the prion form of Ure2 loses the regulatory function, but the enzymatic function appears to be maintained. A number of factors are found to affect the prion properties of Ure2, including mutation and expression levels of molecular chaperones, and the effect of these factors on structure and stability are being investigated. The relationship between structure, function and folding for the yeast prion Ure2 are discussed.

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Section: Chaperonesmentioning

confidence: 99%

Section: Chaperonesmentioning

confidence: 99%

Section: Chaperonesmentioning

confidence: 99%

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The yeast prion protein Ure2: Structure, function and folding

Lian

Jiang

Zhang

et al. 2006

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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“…Another remarkable activity of Hsp104p is prion maintenance (Chernoff et al, 1995;Patino et al, 1996;Paushkin et al, 1996;DebBurman et al, 1997;Moriyama et al, 2000). Prions are proteinaceous genetic elements that have the ability to undergo heritable, self-perpetuating changes in conformation.…”

Section: Introductionmentioning

confidence: 99%

“…This explains the observation that Hsp104p is not required for normal growth, or even growth at high temperatures, but is vital for surviving extreme conditions. The relationship between Hsp104p and thermotolerance is simple and direct: the more Hsp104p present, the higher the level of thermotolerance.Another remarkable activity of Hsp104p is prion maintenance (Chernoff et al, 1995;Patino et al, 1996;Paushkin et al, 1996;DebBurman et al, 1997;Moriyama et al, 2000). Prions are proteinaceous genetic elements that have the ability to undergo heritable, self-perpetuating changes in conformation.…”

mentioning

confidence: 99%

Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region

Schirmer

Homann

Kowal

et al. 2004

MBoC

108

111

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Heat-shock protein 104 (Hsp104p) is a protein-remodeling factor that promotes survival after extreme stress by disassembling aggregated proteins and can either promote or prevent the propagation of prions (protein-based genetic elements). Hsp104p can be greatly overexpressed without slowing growth, suggesting tight control of its powerful protein-remodeling activities. We isolated point mutations in Hsp104p that interfere with this control and block cell growth. Each mutant contained alterations in the middle region (MR). Each of the three MR point mutations analyzed in detail had distinct phenotypes. In combination with nucleotide binding site mutations, Hsp104p T499I altered bud morphology and caused septin mislocalization, colocalizing with the misplaced septins. Point mutations in the septin Cdc12p suppressed this phenotype, suggesting that it is due to direct Hsp104p-septin interactions. Hsp104p A503V did not perturb morphology but stopped cell growth. Remarkably, when expressed transiently, the mutant protein promoted survival after extreme stress as effectively as did wild-type Hsp104p. Hsp104p A509D had no deleterious effects on growth or morphology but had a greatly reduced ability to promote thermotolerance. That mutations in an 11-amino acid stretch of the MR have such profound and diverse effects suggests the MR plays a central role in regulating Hsp104p function. INTRODUCTIONThe AAA ϩ proteins are ATPases associated with various cellular activities. They are important proteins with a great diversity of functions, including protein folding, membrane trafficking, organelle biogenesis, proteolysis, intracellular motility, and DNA replication (Neuwald et al., 1999;Vale, 2000;Ogura and Wilkinson, 2001). Little is known about how most AAA ϩ proteins recognize substrates and use ATP binding and hydrolysis to remodel them. The intrinsic complexity and multiplicity of conformational states of the AAA ϩ proteins make them difficult to study. The Clp/ HSP100 proteins are members of the AAA ϩ superfamily and have been the subject of intense biochemical analysis in vitro and genetic analysis in vivo (Wickner et al., 1999;Glover and Tkach, 2001). The functional unit of the yeast HSP100 heatshock protein 104 (Hsp104p) is composed of six monomers, each with two ATP binding sites (nucleotide binding domains one and two; NBD1 and NBD2) flanked by aminoterminal, middle, and carboxy-terminal regions (Figure 1).Hsp104p has remarkable functions, one of which is to allow survival after extreme stress. For example, yeast cells expressing Hsp104p are 1000 times more viable after exposure to temperatures Ն50°C or to an ethanol concentration of 20% than cells carrying deletions of HSP104 (Sanchez and Lindquist, 1990;Sanchez et al., 1992). This survival capacity is directly attributable to Hsp104p's ability to resolubilize protein aggregates and, together with Hsp70p and Hsp40p, return them to their folded and active states (Parsell et al., 1994;Glover and Lindquist, 1998;Goloubinoff et al., 1999). This is in contrast to other...

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Prions as Epigenetic Regulators of Phenotype in Fungi

Naeimi

Tuite

2012

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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[URE3] Prion Propagation in Saccharomyces cerevisiae: Requirement for Chaperone Hsp104 and Curing by Overexpressed Chaperone Ydj1p

Cited by 259 publications

References 58 publications

The yeast prion protein Ure2: Structure, function and folding

The yeast prion protein Ure2: Structure, function and folding

Dominant Gain-of-Function Mutations in Hsp104p Reveal Crucial Roles for the Middle Region

Prions as Epigenetic Regulators of Phenotype in Fungi

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