Channel mutations in Hsp104 hexamer distinctively affect thermotolerance and prion‐specific propagation

Kurahashi, Hiroshi; Nakamura, Yoshikazu

doi:10.1111/j.1365-2958.2007.05629.x

Cited by 47 publications

(66 citation statements)

References 56 publications

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“…However, the mutant was also insoluble when shuffled through a [rnq -] strain, indicating that the aggregation of Rnq1p-L94A is non-specific (Fig. 8A) 20,25,[28][29][30][31] These mutations are found throughout the protein and may interfere with Hsp104p activity at a variety of different steps including substrate recognition, hexamer formation and nucleotide hydrolysis. Thus, there are many targets within Hsp104p that can be altered and cause the loss of prion propagation.…”

Section: Introductionmentioning

confidence: 99%

“…23,26,27 Due to the discrete nature of the domains, a variety of mutations have been described in each domain of Hsp104p that affect prion propagation. 20,25,[28][29][30][31] One model of Hsp104p function in prion biology posits that Hsp104p has two roles in prion maintenance: generation of transmissible material (seeds) from prion aggregates and conversion of monomer into a prion-competent form. 17,[32][33][34] A complete loss of Hsp104p activity eliminates (cures) all known yeast prions.…”

Section: Introductionmentioning

confidence: 99%

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Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Bardill

Dulle²,

Fisher³

et al. 2009

Prion

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Bardill

Dulle²,

Fisher³

et al. 2009

Prion

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“…Although protein disaggregation activity of Hsp104 is required for both thermotolerance and prion propagation, we and others have identified mutations in Hsp104 that affect these processes separately (27,32,39,60). The ability of Hsp104 to thread proteins through its central pore, however, is required for both processes (29,41,68), so this distinction in Hsp104 function could be due to differences in how Hsp104 interacts with amorphous aggregates of thermally denatured proteins and highly ordered prion aggregates or with cofactors that interact with the different prions as substrates.…”

mentioning

confidence: 99%

Sti1 Regulation of Hsp70 and Hsp90 Is Critical for Curing of Saccharomyces cerevisiae [PSI⁺] Prions by Hsp104

Reidy

Masison

2010

Molecular and Cellular Biology

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Although propagation ofor Hsp90 interaction cured less efficiently, and the Hsp90 inhibitor radicicol abolished curing, implying that Sti1 acts in curing through Hsp70 and Hsp90 interactions. Accordingly, strains lacking constitutive or inducible Hsp90 isoforms cured at reduced rates. We confirm an earlier finding that elevating free ubiquitin levels enhances curing, but it did not overcome inhibition of curing caused by Hsp90 defects, suggesting that Hsp90 machinery is important for the contribution of ubiquitin to curing. We also find curing associated with cell division. Our findings point to crucial roles of Hsp70, Sti1, and Hsp90 for efficient curing by overexpressed Hsp104 and provide evidence supporting the earlier suggestion that destruction of prions by protein disaggregation does not adequately explain the curing.

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“…When Sup35 is in the [PSI ϩ ] state, ribosomes often fail to release polypeptides at stop codons, causing a non-Mendelian trait to appear that is easily detected by nonsense suppression (23,29,30). To uncover host factors responsible for [PSI ϩ ] propagation, we have developed a genome-wide genetic selection method for [PSI ϩ ]-eliminating factors or mutants by use of the chromosomal ura3-197 mutant (21). Based on this selection system, we have selected host factors whose high-level expression on a multicopy plasmid leads to [PSI ϩ ] elimination.…”

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confidence: 99%

A Regulatory Role of the Rnq1 Nonprion Domain for Prion Propagation and Polyglutamine Aggregates

Kurahashi

Ishiwata

Shibata

et al. 2008

Molecular and Cellular Biology

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Prions are transmissible agents caused by the self-propagating conformational change of proteins (32). Prions appear to be amyloid protein aggregates that propagate by capturing soluble proteins and converting them into an infectious aggregated form (33). According to the "protein only" hypothesis (32), the prion protein (PrP) is the sole agent responsible for causing numerous infectious diseases, including scrapie (sheep), bovine spongiform encephalopathy (cow), and chronic wasting disease (deer and elk) as well as kuru and Creutzfeld-Jacob disease (humans Het-s] in Podospora anserina, have also been characterized as non-Mendelian inheritable elements (7,37,43). Molecular and genetic studies of these fungal prions have greatly facilitated the elucidation of the molecular basis for prion conversion and propagation as well as the general criteria for prionogenicity in a protein's primary structure.[PSI ϩ ] is a prion form of Sup35, which is the eRF3 polypeptide release factor that is essential for terminating protein synthesis at stop codons (39, 45; for a review, see reference 17). When Sup35 is in the [PSI ϩ ] state, ribosomes often fail to release polypeptides at stop codons, causing a non-Mendelian trait to appear that is easily detected by nonsense suppression (23,29,30). To uncover host factors responsible for [PSI ϩ ] propagation, we have developed a genome-wide genetic selection method for [PSI ϩ ]-eliminating factors or mutants by use of the chromosomal ura3-197 mutant (21). Based on this selection system, we have selected host factors whose high-level expression on a multicopy plasmid leads to [PSI ϩ ] elimination. One clone yielded Rnq1⌬100, an N-terminal truncation of Rnq1, and is further examined in this study. Although there are some reports that the maintenance or de novo appearance of one prion is affected by several genetic manipulations such as overexpression of its own prion domain (15, 16), heterologous prion variants (5, 35), or nonprion protein mutants (1), the molecular basis of the action of one prion in inhibiting heterologous prions is not known.Rnq1 is a protein of unknown function and is one of several known yeast proteins containing a QN-rich prion domain, where the name derives from "rich in asparagine (N) and glutamine (Q)" (37 . According to the seeding model, a heterologous preexisting protein in the prion conformation is used as a template for the conversion of Sup35 into its prion form, which then proceeds to seed its own rapid and separate aggregation. Importantly, [PIN ϩ ] also facilitates the de novo appearance of the prion [URE3] and promotes polyglutamine (polyQ) aggregation and toxicity in general (5,25,27). Therefore, the seeding model predicts that [PIN ϩ ] aggregates provide a "friendly" nidus on which the first seeds of a heterologous prion or polyQ amyloid can form (11,41). The alternative titration model postulates that preexisting heterologous prions or prion-like aggregates capture and inactivate an inhibitor that prevents conversion of Sup35 into a

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Channel mutations in Hsp104 hexamer distinctively affect thermotolerance and prion‐specific propagation

Cited by 47 publications

References 56 publications

Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Sti1 Regulation of Hsp70 and Hsp90 Is Critical for Curing of Saccharomyces cerevisiae [PSI⁺] Prions by Hsp104

A Regulatory Role of the Rnq1 Nonprion Domain for Prion Propagation and Polyglutamine Aggregates

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Channel mutations in Hsp104 hexamer distinctively affect thermotolerance and prion‐specific propagation

Cited by 47 publications

References 56 publications

Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

Sti1 Regulation of Hsp70 and Hsp90 Is Critical for Curing of Saccharomyces cerevisiae [PSI+] Prions by Hsp104

A Regulatory Role of the Rnq1 Nonprion Domain for Prion Propagation and Polyglutamine Aggregates

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Sti1 Regulation of Hsp70 and Hsp90 Is Critical for Curing of Saccharomyces cerevisiae [PSI⁺] Prions by Hsp104