<i>De Novo</i> Appearance and “Strain” Formation of Yeast Prion [<i>PSI</i>+] Are Regulated by the Heat-Shock Transcription Factor

Park, Kyung Won; Hahn, Ji Sook; Fan, Qing; Thiele, Dennis J.; Li, Liming

doi:10.1534/genetics.105.054221

Cited by 31 publications

(37 citation statements)

References 74 publications

(74 reference statements)

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“…Alterations of the heat-shock factor (Hsf), which regulates Hsp expression, influence de novo [PSI + ] appearance. Depending on the Hsf domain altered, these mutations can increase or decrease the frequency of [PSI + ] appearance and change the spectrum of the de novo-induced [PSI + ] variants (Park et al 2006). Hsp104 was implicated in the promotion of amyloid formation by excess Sup35NM in vitro (Shorter and Lindquist 2004), although this effect could be due to multiplying the initially formed nuclei via fragmentation.…”

Section: Other Host Effects On Prion Formationmentioning

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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Section: Other Host Effects On Prion Formationmentioning

confidence: 99%

Prions in Yeast

2012

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“…We have recently reported that two truncation mutants of the heat-shock transcription factor (HSF) strongly influence ½PSI 1 initiation. An HSF mutant lacking the carboxyl-terminal activation domain, DCTA-HSF, dramatically increases ½PSI 1 de novo formation, whereas a mutant lacking the aminoterminal activation domain, DNTA-HSF, severely inhibits this process (Park et al 2006). Interestingly, DCTA-HSF preferentially allows the formation of weak and mosaic ½PSI 1 variants (Park et al 2006).…”

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The Role of Sse1 in the de Novo Formation and Variant Determination of the [PSI+] Prion

Fan

Park

et al. 2007

Genetics

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Yeast prions are a group of non-Mendelian genetic elements transmitted as altered and self-propagating conformations. Extensive studies in the last decade have provided valuable information on the mechanisms responsible for yeast prion propagation. How yeast prions are formed de novo and what cellular factors are required for determining prion ''strains'' or variants-a single polypeptide capable of existing in multiple conformations to result in distinct heritable phenotypes-continue to defy our understanding. We report here that Sse1, the yeast ortholog of the mammalian heat-shock protein 110 (Hsp110) and a nucleotide exchange factor for Hsp70 proteins, plays an important role in regulating ½PSI

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“…Although a number of mutagenic (Young and Cox, 1971;Jung et al, 2000), overexpression (Chernoff et al, 1993;Chernoff et al, 1995;Kryndushkin et al, 2002), and interaction screens (Bailleul et al, 1999) have been conducted to date, additional factors impacting prion propagation continue to be identified by candidate gene approaches (Chernoff et al, , 2003Newman et al, 1999;Ganusova et al, 2006;Park et al, 2006;Fan et al, 2007;Kryndushkin and Wickner, 2007;Sadlish et al, 2008), suggesting that our current understanding of prion cycle regulation in vivo is incomplete.…”

Section: Introductionmentioning

confidence: 99%

“…Much of our mechanistic understanding of the Sup35/ [PSI ϩ ] in vivo prion cycle has its origins in a variety of genetic screens, which identified key modulators of this process. Although a number of mutagenic (Young and Cox, 1971;Jung et al, 2000), overexpression (Chernoff et al, 1993;Chernoff et al, 1995;Kryndushkin et al, 2002), and interaction screens (Bailleul et al, 1999) have been conducted to date, additional factors impacting prion propagation continue to be identified by candidate gene approaches (Chernoff et al, , 2003Newman et al, 1999;Ganusova et al, 2006;Park et al, 2006;Fan et al, 2007;Kryndushkin and Wickner, 2007;Sadlish et al, 2008), suggesting that our current understanding of prion cycle regulation in vivo is incomplete.In an attempt to elucidate additional factors and processes governing efficient prion propagation in vivo, we took advantage of the fact that N-terminal acetylation is critical for the normal function of many proteins (Polevoda and Sherman, 2003). Approximately 50% of the yeast proteome is cotranslationally acetylated on its N-terminus by the collective action of three enzyme complexes: NatA, NatB, and NatC (Polevoda and Sherman, 2003).…”

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The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype

Pezza

Langseth

Yamamoto

et al. 2009

MBoC

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Protein-only (prion) epigenetic elements confer unique phenotypes by adopting alternate conformations that specify new traits. Given the conformational flexibility of prion proteins, protein-only inheritance requires efficient self-replication of the underlying conformation. To explore the cellular regulation of conformational self-replication and its phenotypic effects, we analyzed genetic interactions between [PSI ؉ ], a prion form of the S. cerevisiae Sup35 protein (Sup35 [PSI ؉ ] ), and the three N ␣ -acetyltransferases, NatA, NatB, and NatC, which collectively modify ϳ50% of yeast proteins. Although prion propagation proceeds normally in the absence of NatB or NatC, the [PSI ؉ ] phenotype is reversed in strains lacking NatA. Despite this change in phenotype, [PSI ؉ ] NatA mutants continue to propagate heritable Sup35 [PSI ؉ ] . This uncoupling of protein state and phenotype does not arise through a decrease in the number or activity of prion templates (propagons) or through an increase in soluble Sup35. Rather, NatA null strains are specifically impaired in establishing the translation termination defect that normally accompanies Sup35 incorporation into prion complexes. The NatA effect cannot be explained by the modification of known components of the [PSI ؉ ] prion cycle including Sup35; thus, novel acetylated cellular factors must act to establish and maintain the tight link between Sup35 [PSI ؉ ] complexes and their phenotypic effects. INTRODUCTIONThe transmission of phenotypes from one individual to another is a fundamental process in biology. Much of our understanding of these events arises from decades of study on nucleic acid metabolism, but new traits may also be passed between individuals without changes in nucleic acid content through a number of epigenetic mechanisms. One particularly intriguing example of such a process is the prion phenomenon, in which the activity of a protein is altered in a heritable way to transmit a new phenotype. How is such a feat accomplished? In 1967, Griffith proposed that some proteins, now known as prions (Prusiner, 1982), can adopt more than one stable form in vivo (Griffith, 1967). Since a protein's structure determines its function, two cells containing the same protein but in diffrent physical states will have distinct phenotypes. This protein-based process has been linked to a number of previously inexplicable events, including the development and spread of the transmissible spongiform encephalopathies in mammals (Prusiner, 1982) and the non-Mendelian inheritance of some traits in fungi (Wickner, 1994).Protein-based traits can only become transmissible, however, if the inherent structural flexibility of prion proteins can be constrained by regulatory mechanisms to create an epigenetic element. For example, if each newly synthesized prion polypeptide chain independently folded to a unique form, all cells would display the same phenotype, which would reflect the average of the accessible states. The appearance of distinct protein-based phenotypes suggests that ...

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De Novo Appearance and “Strain” Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor

Cited by 31 publications

References 74 publications

Prions in Yeast

Prions in Yeast

The Role of Sse1 in the de Novo Formation and Variant Determination of the [PSI+] Prion

The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype

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De Novo Appearance and “Strain” Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor

Cited by 31 publications

References 74 publications

Prions in Yeast

Prions in Yeast

The Role of Sse1 in the de Novo Formation and Variant Determination of the [PSI+] Prion

The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI+] Phenotype

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The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype