DOI: 10.1111/j.1365-2958.2009.06836.x. Sequestration of essential proteins causes prion associated toxicity in yeast

Sequestration of essential proteins causes prion associated toxicity in yeast

10.1111/j.1365-2958.2009.06836.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryPrions are infectious, aggregated proteins that cause diseases in mammals but are not normally toxic in fungi. Excess Sup35p, an essential yeast protein that can exist as the [PSI+] prion, inhibits growth of [PSI+] but not [psi‐] cells. This toxicity is rescued by expressing the Sup35Cp domain of Sup35p, which is sufficient for cell viability but not prion propagation. We now show that rescue requires Sup35Cp levels to be proportional to Sup35p overexpression. Overexpression of Sup35p appeared to cause pre‐existing [PSI+] aggregates to coalesce into larger aggregates, but these were not toxic per se because they formed even when Sup35Cp rescued growth. Overexpression of Sup45p, but not other tested essential Sup35p binding partners, caused rescue. Sup45–GFPp formed puncta that colocalized with large [PSI+] Sup35‐RFPp aggregates in cells overexpressing Sup35p, and the frequency of the Sup45–GFPp puncta was reduced by rescuing levels of Sup35Cp. In contrast, [PSI+] toxicity caused by a high excess of the Sup35p prion domain (Sup35NMp) was rescued by a single copy of Sup35Cp, was not rescued by Sup45p overexpression and was not associated with the appearance of Sup45–GFPp puncta. This suggests [PSI+] toxicity caused by excess Sup35p verses Sup35NMp is, respectively, through sequestration/inactivation of Sup45p verses Sup35p.

Bibliography

Vishveshwara, N., Bradley, M. E., & Liebman, S. W. (2009). Sequestration of essential proteins causes prion associated toxicity in yeast. Molecular Microbiology, 73(6), 1101â1114. Portico.

Authors 3

Namitha Vishveshwara (first)
Michael E. Bradley (additional)
Susan W. Liebman (additional)

References 69 Referenced 65

10.1016/j.cell.2006.04.035
10.1038/nature02998
10.1074/jbc.M410611200
10.1091/mbc.E08-01-0078
10.1017/S1355838200000777
10.1038/375698a0
10.1111/j.1365-2958.2003.03955.x
10.1073/pnas.152330699
10.1385/0-89603-342-2:223
10.1093/bmb/66.1.109
10.1038/nature05294
10.1007/BF00351802
10.1126/science.7754373
10.1128/MCB.22.10.3301-3315.2002
10.1038/hdy.1965.65
10.1093/genetics/128.3.513 / Genetics / Interaction of the yeast omnipotent suppressors SUP1 (SUP45) and SUP2 (SUP35) with non‐mendelian factors by Dagkesamanskaya A.R. (1991)
10.1016/S0092-8674(00)81467-1
10.1093/genetics/144.4.1375
10.1093/genetics/147.2.507
10.1073/pnas.95.5.2400
10.1093/emboj/19.9.1942
10.1016/S0092-8674(01)00427-5
10.1073/pnas.0404968101
10.1073/pnas.0802593105
{'key': 'e_1_2_6_26_1', 'first-page': '334', 'article-title': 'Eukaryotic polypeptide chain release factor eRF3 is an eRF1‐ and ribosome‐dependent guanosine triphosphatase', 'volume': '2', 'author': 'Frolova L.X.', 'year': '1996', 'journal-title': 'RNA'} / RNA / Eukaryotic polypeptide chain release factor eRF3 is an eRF1‐ and ribosome‐dependent guanosine triphosphatase by Frolova L.X. (1996)
10.1128/MCB.26.2.617-629.2006 / Mol Cell Biol / Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast by Ganusova E.E. (2006)
10.1093/emboj/20.8.1993
10.1111/j.1460-9568.2008.06310.x
10.1126/science.1134641
10.1038/nrm2101
10.1016/j.nbd.2006.04.011
10.1128/MCB.02448-05
10.1038/nature02391
10.1038/nature03679
10.1073/pnas.252652099
10.1126/science.1056784
10.1056/NEJM2003ra020003
10.1371/journal.pbio.0020086
10.1073/pnas.90.23.10962
10.1126/science.273.5275.622
10.1002/j.1460-2075.1996.tb00675.x
10.1128/MCB.17.5.2798
10.1126/science.6801762
10.1002/jnr.20025
10.1016/S0092-8674(00)81163-0
10.1038/nm1066
10.1038/ncb1105-1039
10.1128/MCB.24.17.7769-7778.2004
10.1128/MCB.22.13.4723-4738.2002
10.1038/nature03981
10.1371/journal.pbio.0050024
10.1128/MCB.21.20.7035-7046.2001 / Mol Cel Biol / Induction of distinct [URE3] yeast prion strains by Schlumpberger M. (2001)
{'key': 'e_1_2_6_54_1', 'volume-title': 'Methods in Yeast Genetics.', 'author': 'Sherman F.', 'year': '1986'} / Methods in Yeast Genetics. by Sherman F. (1986)
10.1093/genetics/122.1.19
10.1016/S1097-2765(00)80412-8
10.1016/S0092-8674(00)80667-4
10.1002/j.1460-2075.1995.tb00111.x
10.1038/nature02392
10.1371/journal.pgen.1000382
10.1126/science.1067122
10.1111/j.1365-2958.1993.tb01159.x
10.1093/genetics/137.3.671
10.1038/nature06108
10.1093/emboj/20.22.6236
10.1111/j.1365-2958.2004.04157.x
10.1126/science.7909170
{'key': 'e_1_2_6_68_1', 'first-page': '305', 'volume-title': 'Prion Biology and Diseases.', 'author': 'Wickner R.B.', 'year': '2004'} / Prion Biology and Diseases. by Wickner R.B. (2004)
10.1093/emboj/18.5.1182
10.1046/j.1365-2958.2001.02224.x

Dates

Type	When
Created	16 years ago (Aug. 11, 2009, 1:46 p.m.)
Deposited	1 year, 11 months ago (Sept. 28, 2023, 10:12 p.m.)
Indexed	4 months, 4 weeks ago (April 9, 2025, 7:24 p.m.)
Issued	16 years ago (Sept. 1, 2009)
Published	16 years ago (Sept. 1, 2009)
Published Online	15 years, 11 months ago (Sept. 14, 2009)
Published Print	16 years ago (Sept. 1, 2009)

Funders 0

None

BibTeX

@article{Vishveshwara_2009, title={Sequestration of essential proteins causes prion associated toxicity in yeast}, volume={73}, ISSN={1365-2958}, url={http://dx.doi.org/10.1111/j.1365-2958.2009.06836.x}, DOI={10.1111/j.1365-2958.2009.06836.x}, number={6}, journal={Molecular Microbiology}, publisher={Wiley}, author={Vishveshwara, Namitha and Bradley, Michael E. and Liebman, Susan W.}, year={2009}, month=sep, pages={1101–1114} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        4,
        9
      ]
    ],
    "date-time": "2025-04-09T23:24:45Z",
    "timestamp": 1744241085207
  },
  "reference-count": 69,
  "publisher": "Wiley",
  "issue": "6",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2009,
            8,
            11
          ]
        ],
        "date-time": "2009-08-11T00:00:00Z",
        "timestamp": 1249948800000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2009,
        9
      ]
    ]
  },
  "abstract": "<jats:title>Summary</jats:title><jats:p>Prions are infectious, aggregated proteins that cause diseases in mammals but are not normally toxic in fungi. Excess Sup35p, an essential yeast protein that can exist as the [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] prion, inhibits growth of [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] but not [<jats:italic>psi</jats:italic><jats:sup>\u2010</jats:sup>] cells. This toxicity is rescued by expressing the Sup35Cp domain of Sup35p, which is sufficient for cell viability but not prion propagation. We now show that rescue requires Sup35Cp levels to be proportional to Sup35p overexpression. Overexpression of Sup35p appeared to cause pre\u2010existing [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] aggregates to coalesce into larger aggregates, but these were not toxic <jats:italic>per se</jats:italic> because they formed even when Sup35Cp rescued growth. Overexpression of Sup45p, but not other tested essential Sup35p binding partners, caused rescue. Sup45\u2013GFPp formed puncta that colocalized with large [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] Sup35\u2010RFPp aggregates in cells overexpressing Sup35p, and the frequency of the Sup45\u2013GFPp puncta was reduced by rescuing levels of Sup35Cp. In contrast, [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] toxicity caused by a high excess of the Sup35p prion domain (Sup35NMp) was rescued by a single copy of Sup35Cp, was not rescued by Sup45p overexpression and was not associated with the appearance of Sup45\u2013GFPp puncta. This suggests [<jats:italic>PSI</jats:italic><jats:sup>+</jats:sup>] toxicity caused by excess Sup35p verses Sup35NMp is, respectively, through sequestration/inactivation of Sup45p verses Sup35p.</jats:p>",
  "DOI": "10.1111/j.1365-2958.2009.06836.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2009,
        8,
        11
      ]
    ],
    "date-time": "2009-08-11T17:46:50Z",
    "timestamp": 1250012810000
  },
  "page": "1101-1114",
  "source": "Crossref",
  "is-referenced-by-count": 65,
  "title": "Sequestration of essential proteins causes prion associated toxicity in yeast",
  "prefix": "10.1111",
  "volume": "73",
  "author": [
    {
      "given": "Namitha",
      "family": "Vishveshwara",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Michael E.",
      "family": "Bradley",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Susan W.",
      "family": "Liebman",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2009,
        9,
        14
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2006.04.035"
    },
    {
      "key": "e_1_2_6_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature02998"
    },
    {
      "key": "e_1_2_6_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M410611200"
    },
    {
      "key": "e_1_2_6_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.E08-01-0078"
    },
    {
      "key": "e_1_2_6_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1017/S1355838200000777"
    },
    {
      "key": "e_1_2_6_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/375698a0"
    },
    {
      "key": "e_1_2_6_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2958.2003.03955.x"
    },
    {
      "key": "e_1_2_6_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.152330699"
    },
    {
      "key": "e_1_2_6_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1385/0-89603-342-2:223"
    },
    {
      "key": "e_1_2_6_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/bmb/66.1.109"
    },
    {
      "key": "e_1_2_6_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature05294"
    },
    {
      "key": "e_1_2_6_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00351802"
    },
    {
      "key": "e_1_2_6_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7754373"
    },
    {
      "key": "e_1_2_6_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.22.10.3301-3315.2002"
    },
    {
      "key": "e_1_2_6_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/hdy.1965.65"
    },
    {
      "key": "e_1_2_6_17_1",
      "doi-asserted-by": "crossref",
      "first-page": "513",
      "DOI": "10.1093/genetics/128.3.513",
      "article-title": "Interaction of the yeast omnipotent suppressors SUP1 (SUP45) and SUP2 (SUP35) with non\u2010mendelian factors",
      "volume": "128",
      "author": "Dagkesamanskaya A.R.",
      "year": "1991",
      "journal-title": "Genetics"
    },
    {
      "key": "e_1_2_6_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81467-1"
    },
    {
      "key": "e_1_2_6_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/144.4.1375"
    },
    {
      "key": "e_1_2_6_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/147.2.507"
    },
    {
      "key": "e_1_2_6_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.95.5.2400"
    },
    {
      "key": "e_1_2_6_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/19.9.1942"
    },
    {
      "key": "e_1_2_6_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(01)00427-5"
    },
    {
      "key": "e_1_2_6_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0404968101"
    },
    {
      "key": "e_1_2_6_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0802593105"
    },
    {
      "key": "e_1_2_6_26_1",
      "first-page": "334",
      "article-title": "Eukaryotic polypeptide chain release factor eRF3 is an eRF1\u2010 and ribosome\u2010dependent guanosine triphosphatase",
      "volume": "2",
      "author": "Frolova L.X.",
      "year": "1996",
      "journal-title": "RNA"
    },
    {
      "key": "e_1_2_6_27_1",
      "doi-asserted-by": "crossref",
      "first-page": "617",
      "DOI": "10.1128/MCB.26.2.617-629.2006",
      "article-title": "Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast",
      "volume": "2",
      "author": "Ganusova E.E.",
      "year": "2006",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "e_1_2_6_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/20.8.1993"
    },
    {
      "key": "e_1_2_6_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1460-9568.2008.06310.x"
    },
    {
      "key": "e_1_2_6_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1134641"
    },
    {
      "key": "e_1_2_6_31_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrm2101"
    },
    {
      "key": "e_1_2_6_32_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.nbd.2006.04.011"
    },
    {
      "key": "e_1_2_6_33_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.02448-05"
    },
    {
      "key": "e_1_2_6_34_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature02391"
    },
    {
      "key": "e_1_2_6_35_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature03679"
    },
    {
      "key": "e_1_2_6_36_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.252652099"
    },
    {
      "key": "e_1_2_6_37_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1056784"
    },
    {
      "key": "e_1_2_6_38_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM2003ra020003"
    },
    {
      "key": "e_1_2_6_39_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.pbio.0020086"
    },
    {
      "key": "e_1_2_6_40_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.23.10962"
    },
    {
      "key": "e_1_2_6_41_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.273.5275.622"
    },
    {
      "key": "e_1_2_6_42_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1996.tb00675.x"
    },
    {
      "key": "e_1_2_6_43_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.17.5.2798"
    },
    {
      "key": "e_1_2_6_44_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.6801762"
    },
    {
      "key": "e_1_2_6_45_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jnr.20025"
    },
    {
      "key": "e_1_2_6_46_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81163-0"
    },
    {
      "key": "e_1_2_6_47_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm1066"
    },
    {
      "key": "e_1_2_6_48_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ncb1105-1039"
    },
    {
      "key": "e_1_2_6_49_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.24.17.7769-7778.2004"
    },
    {
      "key": "e_1_2_6_50_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.22.13.4723-4738.2002"
    },
    {
      "key": "e_1_2_6_51_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature03981"
    },
    {
      "key": "e_1_2_6_52_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.pbio.0050024"
    },
    {
      "key": "e_1_2_6_53_1",
      "doi-asserted-by": "crossref",
      "first-page": "7035",
      "DOI": "10.1128/MCB.21.20.7035-7046.2001",
      "article-title": "Induction of distinct [URE3] yeast prion strains",
      "volume": "20",
      "author": "Schlumpberger M.",
      "year": "2001",
      "journal-title": "Mol Cel Biol"
    },
    {
      "key": "e_1_2_6_54_1",
      "volume-title": "Methods in Yeast Genetics.",
      "author": "Sherman F.",
      "year": "1986"
    },
    {
      "key": "e_1_2_6_55_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/122.1.19"
    },
    {
      "key": "e_1_2_6_56_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(00)80412-8"
    },
    {
      "key": "e_1_2_6_57_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80667-4"
    },
    {
      "key": "e_1_2_6_58_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1995.tb00111.x"
    },
    {
      "key": "e_1_2_6_59_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature02392"
    },
    {
      "key": "e_1_2_6_60_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1371/journal.pgen.1000382"
    },
    {
      "key": "e_1_2_6_61_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1067122"
    },
    {
      "key": "e_1_2_6_62_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2958.1993.tb01159.x"
    },
    {
      "key": "e_1_2_6_63_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/137.3.671"
    },
    {
      "key": "e_1_2_6_64_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature06108"
    },
    {
      "key": "e_1_2_6_65_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/20.22.6236"
    },
    {
      "key": "e_1_2_6_66_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2958.2004.04157.x"
    },
    {
      "key": "e_1_2_6_67_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7909170"
    },
    {
      "key": "e_1_2_6_68_1",
      "first-page": "305",
      "volume-title": "Prion Biology and Diseases.",
      "author": "Wickner R.B.",
      "year": "2004"
    },
    {
      "key": "e_1_2_6_69_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/18.5.1182"
    },
    {
      "key": "e_1_2_6_70_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2958.2001.02224.x"
    }
  ],
  "container-title": "Molecular Microbiology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2958.2009.06836.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2958.2009.06836.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        9,
        29
      ]
    ],
    "date-time": "2023-09-29T02:12:03Z",
    "timestamp": 1695953523000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2009.06836.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2009,
        9
      ]
    ]
  },
  "references-count": 69,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          2009,
          9
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1111/j.1365-2958.2009.06836.x"
  ],
  "URL": "http://dx.doi.org/10.1111/j.1365-2958.2009.06836.x",
  "relation": {},
  "ISSN": [
    "0950-382X",
    "1365-2958"
  ],
  "subject": [],
  "container-title-short": "Molecular Microbiology",
  "published": {
    "date-parts": [
      [
        2009,
        9
      ]
    ]
  }
}