ArticlePloS one2013
The Type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 80 citations in OpenAlex.
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- N-recognins UBR1 and UBR2 as central ER stress sensors in mammals.Molecules and cells · 2024Article
- Large-scale identification of genes involved in septal pore plugging in multicellular fungi.Nature communications · 2023Article
- Identification of subfunctionalized aggregate-remodeling J-domain proteins in Arabidopsis thaliana.Journal of experimental botany · 2023Article
- HSP70-binding motifs function as protein quality control degrons.Cellular and molecular life sciences : CMLS · 2023Article
- Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome by Tti1, a specialized PIKK chaperone.Molecular biology of the cell · 2022Article
- Quality control of cytoplasmic proteins inside the nucleus.Computational and structural biotechnology journal · 2022Review
- Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control.Biomolecules · 2021Review
- Protein quality control degron-containing substrates are differentially targeted in the cytoplasm and nucleus by ubiquitin ligases.Genetics · 2021Article
- It's not just a phase; ubiquitination in cytosolic protein quality control.Biochemical Society transactions · 2021Review
- Direct involvement of Hsp70 ATP hydrolysis in Ubr1-dependent quality control.Molecular biology of the cell · 2020Article
- Chaperone-Mediated Protein Disaggregation Triggers Proteolytic Clearance of Intra-nuclear Protein Inclusions.Cell reports · 2020Article
- Genetic Selection Based on a Ste6G3 (Bethesda, Md.) · 2020Article
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- Overexpression of Seagrass Nucleotide Exchange Factor GenePlant signaling & behavior · 2020Article
- Post-transcriptional negative feedback regulation of proteostasis through the Dis3 ribonuclease and its disruption by polyQ-expanded Huntingtin.Nucleic acids research · 2019Article
- Recognition and Degradation of Mislocalized Proteins in Health and Disease.Cold Spring Harbor perspectives in biology · 2019Review
- Ubiquitin-dependent protein degradation at the endoplasmic reticulum and nuclear envelope.Seminars in cell & developmental biology · 2019Review
- Article
- Hsp40/70/110 chaperones adapt nuclear protein quality control to serve cytosolic clients.The Journal of cell biology · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mechanisms for cooperation between the cytosolic Hsp70 system and the ubiquitin proteasome system during protein triage are not clear. Herein, we identify new mechanisms for selection of misfolded cytosolic proteins for degradation via defining functional interactions between specific cytosolic Hsp70/Hsp40 pairs and quality control ubiquitin ligases. These studies revolved around the use of S. cerevisiae to elucidate the degradation pathway of a terminally misfolded reporter protein, short-lived GFP (slGFP). The Type I Hsp40 Ydj1 acts with Hsp70 to suppress slGFP aggregation. In contrast, the Type II Hsp40 Sis1 is required for proteasomal degradation of slGFP. Sis1 and Hsp70 operate sequentially with the quality control E3 ubiquitin ligase Ubr1 to target slGFP for degradation. Compromise of Sis1 or Ubr1 function leads slGFP to accumulate in a Triton X-100-soluble state with slGFP degradation intermediates being concentrated into perinuclear and peripheral puncta. Interestingly, when Sis1 activity is low the slGFP that is concentrated into puncta can be liberated from puncta and subsequently degraded. Conversely, in the absence of Ubr1, slGFP and the puncta that contain slGFP are relatively stable. Ubr1 mediates proteasomal degradation of slGFP that is released from cytosolic protein handling centers. Pathways for proteasomal degradation of misfolded cytosolic proteins involve functional interplay between Type II Hsp40/Hsp70 chaperone pairs, PQC E3 ligases, and storage depots for misfolded proteins.
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