Antagonistic Interactions between Yeast [PSI+] and [URE3] Prions and Curing of [URE3] by Hsp70 Protein Chaperone Ssa1p but Not by Ssa2p

Schwimmer, Christine; Masison, Daniel C.

doi:10.1128/mcb.22.11.3590-3598.2002

Cited by 167 publications

(162 citation statements)

References 41 publications

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“…Reported antagonistic interactions between prions also suggest a direct interaction (43,44). Indeed, binding of a Q͞N-rich domain to the growth tip of a heterologous prion seed that could occasionally lead to the formation of a novel prion might also block the propagation of the heterologous seed.…”

Section: Discussionmentioning

confidence: 99%

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Derkatch

Uptain²,

Outeiro³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

204

215

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Section: Discussionmentioning

confidence: 99%

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Derkatch

Uptain²,

Outeiro³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

204

215

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“…Ure2p normally functions as a soluble regulator of nitrogen catabolism (5,6), and its conversion to the aggregated amyloid prion form produces inappropriate derepression of many genes of nitrogen catabolism, resulting in slightly slowed growth (7). Many [URE3] isolates have a severe toxic effect, producing extremely slowed growth (8).…”

Section: T He Yeast Prion [Ure3] Is a Self-propagating Amyloid Of Ure2pmentioning

confidence: 99%

Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants

Wickner

Bezsonov

Bateman

2014

Proc. Natl. Acad. Sci. U.S.A.

120

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[URE3] is an amyloid prion of the Saccharomyces cerevisiae Ure2p, a regulator of nitrogen catabolism. Overproduction of Btn2p, involved in late endosome to Golgi protein transport, or its paralog Cur1p, cures [URE3]. Btn2p, in curing, is colocalized with Ure2p in a single locus, suggesting sequestration of Ure2p amyloid filaments. We find that most [URE3] variants generated in a btn2 cur1 double mutant are cured by restoring normal levels of Btn2p and Cur1p, with both proteins needed for efficient curing. (1-4). Ure2p normally functions as a soluble regulator of nitrogen catabolism (5, 6), and its conversion to the aggregated amyloid prion form produces inappropriate derepression of many genes of nitrogen catabolism, resulting in slightly slowed growth (7). Many [URE3] isolates have a severe toxic effect, producing extremely slowed growth (8). A single protein sequence can assume any of many different heritable/infectious forms with different biological properties and, one infers, different protein conformations. The parallel in-register β-sheet architecture of the [URE3] prion amyloid (9) can explain the templating properties of this prion (10) and the ability of the Ure2p amyloid to act as a gene with multiple alleles (4).[PSI+] is similarly an amyloid prion of Sup35p, a subunit of the translation termination factor [reviewed by Liebman and Chernoff (11)], and [PIN+] is a prion of Rnq1p, a protein of unknown function (12)(13)(14).Eukaryotic cells deal with protein aggregates in several ways, including resolubilization, degradation, sequestration, and combinations of these processes. Several organelles and systems have been recognized to play a role in these processes, including vacuoles (the yeast equivalent of the mammalian lysosomes), the ubiquitin-proteasome systems, the autophagy system, and the various chaperones.In mammalian cells the aggresome is a centrosomal structure to which aggregates are brought in a microtubule-dependent process (15). A yeast site near the spindle pole body (the yeast centrosome) collects huntingtin/polyQ aggregates in a process that depends on microtubule function, suggesting that this is the yeast aggresome (16). Bmh1p, a 14-3-3 protein, was found associated with huntingtin in yeast aggresomes, and bmh1Δ prevented aggresome accumulation of huntingtin (16).Btn2p and Cur1p were found to cure the [URE3] prion when overproduced (17). These proteins are paralogs, members of the Hook family, consistent with their similar effects, but Btn2 localized to a site next to the nucleus, whereas Cur1 was localized largely within the nucleus (17). During the curing process, those [URE3] cells having both Ure2p-GFP aggregates and Btn2-RFP dots show striking colocalization (17-19). Partial colocalization of Btn2-RFP with Sup35NM-GFP in a [PSI+] strain or with the huntingtin-like Q103-GFP were also observed (17), but overexpression of Btn2p or Cur1p did not cure [PSI+]. Doubly deleted btn2Δ cur1Δ strains show an elevated seed number of [URE3] and partial resistance to prion curing by dimethyl sul...

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“…The titration of the chaperones could decrease prion stability. Also, because different prions respond differently to the depletion of various cellular factors, 36 their effects on each other may not be reciprocal.…”

confidence: 99%

“…Finally, the cell may mount a response to the presence of amyloid or amyloid precursors of prions. 36,37 This response is expected to be aimed at prion disaggregation and elimination but may actually facilitate prion transmission, e.g., by breaking prion aggregates into smaller seeds. Such a generic response would affect not only the prion protein that induced it, but other, heterologous prions and prionogenic proteins.…”

confidence: 99%

Prion-Prion Interactions

Derkatch

Liebman²

2007

Prion

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Published previously online as a Prion AbStrActThe term prion has been used to describe self-replicating protein conformations that can convert other protein molecules of the same primary structure into its prion conformation. Several different proteins have now been found to exist as prions in Saccharomyces cerevisiae. Surprisingly, these heterologous prion proteins have a strong influence on each others' appearance and propagation, which may result from structural similarity between the prions. Both positive and negative effects of a prion on the de novo appearance of a heterologous prion have been observed in genetic studies. Other examples of reported interactions include mutual or unilateral inhibition and destabilization when two prions are present together in a single cell. In vitro work showing that one purified prion stimulates the conversion of a purified heterologous protein into a prion form, suggests that facilitation of de novo prion formation by heterologous prions in vivo is a result of a direct interaction between the prion proteins (a cross-seeding mechanism) and does not require other cellular components. However, other cellular structures, e.g., the cytoskeleton, may provide a scaffold for these interactions in vivo and chaperones can further facilitate or inhibit this process. Some negative prion-prion interactions may also occur via a direct interaction between the prion proteins. Another explanation is a competition between the prions for cellular factors involved in prion propagation or differential effects of chaperones stimulated by one prion on the heterologous prions.

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Antagonistic Interactions between Yeast [PSI⁺] and [URE3] Prions and Curing of [URE3] by Hsp70 Protein Chaperone Ssa1p but Not by Ssa2p

Cited by 167 publications

References 41 publications

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants

Prion-Prion Interactions

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Antagonistic Interactions between Yeast [PSI+] and [URE3] Prions and Curing of [URE3] by Hsp70 Protein Chaperone Ssa1p but Not by Ssa2p

Cited by 167 publications

References 41 publications

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI+] prion in yeast and aggregation of Sup35in vitro

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI+] prion in yeast and aggregation of Sup35in vitro

Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants

Prion-Prion Interactions

Contact Info

Product

Resources

About

Antagonistic Interactions between Yeast [PSI⁺] and [URE3] Prions and Curing of [URE3] by Hsp70 Protein Chaperone Ssa1p but Not by Ssa2p

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on thede novoformation of the [PSI⁺] prion in yeast and aggregation of Sup35in vitro