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Hsp70-associated chaperones have a critical role in buffering protein production costs.

Zoltán Farkas | Dorottya Kalapis | Zoltán Bódi | Béla Szamecz | Andreea Daraba | Karola Almási | Károly Kovács | Gábor Boross | Ferenc Pál | Péter Horváth | Tamás Balassa | Csaba Molnár | Aladár Pettkó-Szandtner | Éva Klement | Edit Rutkai | Attila Szvetnik | Balázs Papp | Csaba Pál
eLife | 2018

Proteins are necessary for cellular growth. Concurrently, however, protein production has high energetic demands associated with transcription and translation. Here, we propose that activity of molecular chaperones shape protein burden, that is the fitness costs associated with expression of unneeded proteins. To test this hypothesis, we performed a genome-wide genetic interaction screen in baker's yeast. Impairment of transcription, translation, and protein folding rendered cells hypersensitive to protein burden. Specifically, deletion of specific regulators of the Hsp70-associated chaperone network increased protein burden. In agreement with expectation, temperature stress, increased mistranslation and a chemical misfolding agent all substantially enhanced protein burden. Finally, unneeded protein perturbed interactions between key components of the Hsp70-Hsp90 network involved in folding of native proteins. We conclude that specific chaperones contribute to protein burden. Our work indicates that by minimizing the damaging impact of gratuitous protein overproduction, chaperones enable tolerance to massive changes in genomic expression.

Pubmed ID: 29377792

Associated grants

  • Agency: Magyar Tudományos Akadémia, International
    Id: Bolyai Research Scholarship
  • Agency: Wellcome, International
    Id: WT 084314/Z/07/Z
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00014
  • Agency: Wellcome Trust, United Kingdom
    Id: 084314
  • Agency: Magyar Tudományos Akadémia, International
    Id: Lendület Programme LP 2009-013/2012
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00020
  • Agency: European Research Council, International
    Id: 648364 H2020-ERC-2014-CoG
  • Agency: Magyar Tudományos Akadémia, International
    Id: Lendület Programme LP 2012-32/2016
  • Agency: Magyar Tudományos Akadémia, International
    Id: Postdoctoral Fellowship Programme PD-038/2015
  • Agency: Magyar Tudományos Akadémia, International
    Id: Postdoctoral Fellowship Programme Postdoc2014-85
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00006
  • Agency: Seventh Framework Programme, International
    Id: Initial Training Network METAFLUX 264780
  • Agency: European Research Council, International
    Id: 648364
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00026
  • Agency: Wellcome, International
    Id: WT 098016/Z/11/Z
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00001
  • Agency: Gazdaságfejlesztési és Innovációs Operatív Program, International
    Id: GINOP-2.3.2-15-2016-00032

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