PXD037835-1

PXD037835 is an original dataset announced via ProteomeXchange.

Title	Cellular responses in yeast proteostasis mutants affected in diverse branches of the protein quality control system
Description	Protein quality controls (PQC) systems rely on three main activities to prevent the accumulation of misfolded proteins upon stress conditions and aging: refolding, degradation and sequestration. In Saccharomyces cerevisiae the Hsp70 chaperone system plays a central role in protein refolding, while degradation is predominantly executed by the ubiquitin proteasome system (UPS). The sequestrases Hsp42 and Btn2 deposit misfolded proteins in cytosolic and nuclear inclusions. This activity prevents exhaustion of limited Hsp70 resources by restricting the accessibility of misfolded proteins upon sequestration. Sequestrase mutants therefore show negative genetic interactions with yeast Hsp70 co-chaperone mutants (fes1D hsp104D, DD) that suffer from low Hsp70 capacity. Growth of DDbtn2D mutants is highly temperature-sensitive and results in proteostasis breakdown at non-permissive temperatures. Here, we probed for the role of the UPS system in maintaining protein homeostasis in DDbtn2D cells, affected in two major PQC branches. We show that DDD cells induce expression of diverse stress-related pathways including the UPS to counteract the proteostasis defects. UPS dependent degradation of the stringent Hsp70 substrate Luciferase in the mutant cells mirrors such compensatory activities of the PQC system. However, the enhanced UPS activity does not improve but aggravates the phenotypes of DDbtn2D cells. Reducing UPS activity in the mutant by lowering the levels of functional 26S proteasomes improved growth, increased refolding yield of the Luciferase reporter and attenuated global stress responses. This indicates that an imbalance between Hsp70-dependent refolding and UPS-mediated degradation activities strongly affects protein homeostasis of yeast Hsp70 capacity mutants and contributes to their severe growth phenotypes.
HostingRepository	PRIDE
AnnounceDate	2023-03-11
AnnouncementXML	Submission_2023-03-10_19:00:01.077.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ThomasRuppert
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-31 07:55:51	ID requested
⏵ 1	2023-03-10 19:00:02	announced
2	2023-11-14 08:24:01	announced	2023-11-14: Updated project metadata.

Jawed A, Ho CT, Grousl T, Shrivastava A, Ruppert T, Bukau B, Mogk A, Balanced activities of Hsp70 and the ubiquitin proteasome system underlie cellular protein homeostasis. Front Mol Biosci, 9():1106477(2022) [pubmed]

submitter keyword: chaperone, sequestrases, Hsp70, proteasome, proteostasis

ThomasRuppert
contact affiliation	Core facility for mass spectrometry and proteomics ZMBH, University Heidelberg Im Neuenheimer Feld 282 69120 Heidelberg Germany
contact email	t.ruppert@zmbh.uni-heidelberg.de
lab head
ThomasRuppert
contact affiliation	ZMBH, Im Neuenheimer Feld 282, 69122 Heidelberg
contact email	t.ruppert@zmbh.uni-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037835
     1. Label: PRIDE project
     2. Name: Cellular responses in yeast proteostasis mutants affected in diverse branches of the protein quality control system