To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1

Yury A. Barbitoff, Andrew G. Matveenko, Svetlana E. Moskalenko, Olga M. Zemlyanko, Gary P. Newnam, Ayesha Patel, Tatiana A. Chernova, Yury O. Chernoff, Galina A. Zhouravleva

Research output

8 Citations (Scopus)

Abstract

Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI+]. We demonstrate that both curing of [URE3] and enhancement of [PSI+] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.

Original languageEnglish
Pages (from-to)242-257
Number of pages16
JournalMolecular Microbiology
Volume105
Issue number2
DOIs
Publication statusPublished - Jul 2017

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Prions
Yeasts
Nuclear Localization Signals
Molecular Chaperones
Fungal Proteins
Recycling
Quality Control
Cytoplasm
Proteins

Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

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title = "To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1",
abstract = "Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI+]. We demonstrate that both curing of [URE3] and enhancement of [PSI+] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.",
keywords = "DISEASE-RELATED PROTEIN, RELEASE FACTORS ERF1, SACCHAROMYCES-CEREVISIAE, URE3 PRION, TRANSLATION TERMINATION, ANTAGONISTIC INTERACTIONS, MOLECULAR CHAPERONES, DEPENDENT LETHALITY, SHUTTLE VECTORS, IMAGE-ANALYSIS",
author = "Barbitoff, {Yury A.} and Matveenko, {Andrew G.} and Moskalenko, {Svetlana E.} and Zemlyanko, {Olga M.} and Newnam, {Gary P.} and Ayesha Patel and Chernova, {Tatiana A.} and Chernoff, {Yury O.} and Zhouravleva, {Galina A.}",
year = "2017",
month = "7",
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T1 - To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1 on yeast prions are mediated by the chaperone Sis1

AU - Barbitoff, Yury A.

AU - Matveenko, Andrew G.

AU - Moskalenko, Svetlana E.

AU - Zemlyanko, Olga M.

AU - Newnam, Gary P.

AU - Patel, Ayesha

AU - Chernova, Tatiana A.

AU - Chernoff, Yury O.

AU - Zhouravleva, Galina A.

PY - 2017/7

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AB - Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI+]. We demonstrate that both curing of [URE3] and enhancement of [PSI+] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.

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