A bipolar personality of yeast prion proteins

Kurahashi, Hiroshi; Oishi, Keita; Nakamura, Yoshikazu

doi:10.4161/pri.18307

Cited by 7 publications

(5 citation statements)

References 61 publications

(6 reference statements)

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“…Also, overexpression of two more proteins identified in our screen for [ PIN + ], 12 Lsm4 and New1, was recently shown to cause cells to lose prions 44 , 45 . Similar to our observations for Pin4C, 27 all the above negative interactions are associated with enlargement of aggregates proposed to result from inefficient fragmentation and poor transmission to daughter cells 25 , 42 - 45 . However, while this is consistent with Hsp104 deficiency, a model postulating aggregate enlargement by direct lateral association of heterologous aggregates was favored (Fig.…”

Section: Other Negative Prion-prion Interactions: Applicability Of Tisupporting

confidence: 87%

“…Several negative prion interactions were recently reported by the Nakamura and Yoshida labs 25 . They report curing of one or several yeast prions ([ URE3 ] and, sometimes, [ PSI + ] or [ PIN + ]) by overexpression of Gpg1, a non-Q/N-rich G-protein γ-subunit mimic 42 ; by overexpression of mutant alleles of Rnq1 in [ PIN + ] strains; and by a Rnq1-Δ100 deletion or an array of rnq1 point mutations in the presence of [ PIN + ] 20 - 22 , 43 .…”

Section: Other Negative Prion-prion Interactions: Applicability Of Timentioning

confidence: 89%

“…Consistent with our data, such a small drop in Hsp104 levels is obviously insufficient to cure [ PSI + ], 34 but it may be sufficient for [ URE3 ] destabilization. Indeed, experimental evidence suggests that the number of [ URE3 ] propagons transmissible to daughter cells is less than the number of [ PSI + ] propagons, which could explain why [ URE3 ] is more sensitive to the reduction of aggregate fragmentation and, specifically, to Hsp104 inactivation 25 , 40 , 41 . Thus, we hypothesize that curing of [ URE3 ] by Pin3 is caused by Hsp104 titration (Fig.…”

Section: Other Negative Prion-prion Interactions: Applicability Of Timentioning

confidence: 95%

“…Two principally different mechanisms were proposed for interactions between heterologous prion proteins 12 , 14 , 16 , 18 , 19 , 23 - 25 . The first postulates direct interaction of heterologous prion domains (Fig.…”

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confidence: 99%

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The story of stolen chaperones

Derkatch

Liebman

2013

Prion

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Prions are self-seeding alternate protein conformations. Most yeast prions contain glutamine/asparagine (Q/N)-rich domains that promote the formation of amyloid-like prion aggregates. Chaperones, including Hsp104 and Sis1, are required to continually break these aggregates into smaller “seeds.” Decreasing aggregate size and increasing the number of growing aggregate ends facilitates both aggregate transmission and growth. Our previous work showed that overexpression of 11 proteins with Q/N-rich domains facilitates the de novo aggregation of Sup35 into the [PSI+] prion, presumably by a cross-seeding mechanism. We now discuss our recent paper, in which we showed that overexpression of most of these same 11 Q/N-rich proteins, including Pin4C and Cyc8, destabilized pre-existing Q/N rich prions. Overexpression of both Pin4C and Cyc8 caused [PSI+] aggregates to enlarge. This is incompatible with a previously proposed “capping” model where the overexpressed Q/N-rich protein poisons, or “caps,” the growing aggregate ends. Rather the data match what is expected of a reduction in prion severing by chaperones. Indeed, while Pin4C overexpression does not alter chaperone levels, Pin4C aggregates sequester chaperones away from the prion aggregates. Cyc8 overexpression cures [PSI+] by inducing an increase in Hsp104 levels, as excess Hsp104 binds to [PSI+] aggregates in a way that blocks their shearing.

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Section: Other Negative Prion-prion Interactions: Applicability Of Tisupporting

confidence: 87%

Section: Other Negative Prion-prion Interactions: Applicability Of Timentioning

confidence: 89%

Section: Other Negative Prion-prion Interactions: Applicability Of Timentioning

confidence: 95%

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confidence: 99%

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The story of stolen chaperones

Derkatch

Liebman

2013

Prion

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“…LSM4 directly interacts with PUB1, the third KP/EPD hub, and with two proteins (PUF4 and SCD6) predicted to be prionogenic by PrionScan [15]. Upon overexpression, LSM4 has been shown to form amyloids that play a key role in elimination of the [PSI+] prion from cells [42]–[44]. Also, ‘P-bodies’, which are cytoplasmic RNA granules that contain translationally repressed ribonucleoproteins, can be formed via the N/Q-rich domain of LSM4 [45].…”

Section: Resultsmentioning

confidence: 99%

Interaction Networks of Prion, Prionogenic and Prion-Like Proteins in Budding Yeast, and Their Role in Gene Regulation

Harbi

Harrison

2014

PLoS ONE

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Prions are transmissible, propagating alternative states of proteins. Prions in budding yeast propagate heritable phenotypes and can function in large-scale gene regulation, or in some cases occur as diseases of yeast. Other ‘prionogenic’ proteins are likely prions that have been determined experimentally to form amyloid in vivo, and to have prion-like domains that are able to propagate heritable states. Furthermore, there are over 300 additional ‘prion-like’ yeast proteins that have similar amino-acid composition to prions (primarily a bias for asparagines and glutamines). Here, we examine the protein functional and interaction networks that involve prion, prionogenic and prion-like proteins. Set against a marked overall preference for N/Q-rich prion-like proteins not to interact with each other, we observe a significant tendency of prion/prionogenic proteins to interact with other, N/Q-rich prion-like proteins. This tendency is mostly due to a small number of networks involving the proteins NUP100p, LSM4p and PUB1p. In general, different data analyses of functional and interaction networks converge to indicate a strong linkage of prionogenic and prion-like proteins, to stress-granule assembly and related biological processes. These results further elucidate how prions may impact gene regulation, and reveal a broader horizon for the functional relevance of N/Q-rich prion-like domains.

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Hsp104 as a key modulator of prion-mediated oxidative stress in Saccharomyces cerevisiae

Singh

Saleh

Bhadra

et al. 2013

Biochemical Journal

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Maintenance of cellular redox homoeostasis forms an important part of the cellular defence mechanism and continued cell viability. Despite extensive studies, the role of the chaperone Hsp104 (heat-shock protein of 102 kDa) in propagation of misfolded protein aggregates in the cell and generation of oxidative stress remains poorly understood. Expression of RNQ1-RFP in Saccharomyces cerevisiae cells led to the generation of the prion form of the protein and increased oxidative stress. In the present study, we show that disruption of Hsp104 in an isogenic yeast strain led to solubilization of RNQ1-RFP. This reduced the oxidative stress generated in the cell. The higher level of oxidative stress in the Hsp104-containing (parental) strain correlated with lower activity of almost all of the intracellular antioxidant enzymes assayed. Surprisingly, this did not correspond with the gene expression analysis data. To compensate for the decrease in protein translation induced by a high level of reactive oxygen species, transcriptional up-regulation takes place. This explains the discrepancy observed between the transcription level and functional enzymatic product. Our results show that in a ΔHsp104 strain, due to lower oxidative stress, no such mismatch is observed, corresponding with higher cell viability. Thus Hsp104 is indirectly responsible for enhancing the oxidative stress in a prion-rich environment.

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A bipolar personality of yeast prion proteins

Cited by 7 publications

References 61 publications

The story of stolen chaperones

The story of stolen chaperones

Interaction Networks of Prion, Prionogenic and Prion-Like Proteins in Budding Yeast, and Their Role in Gene Regulation

Hsp104 as a key modulator of prion-mediated oxidative stress in Saccharomyces cerevisiae

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