ArticleMolecular biology of the cell1999
The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast.
Article in Molecular biology of the cell, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
119 citing papers in PubMed, 282 citations in OpenAlex.
- Chromosome duplication causes premature aging via defects in ribosome quality control.PLoS biology · 2025Article
- Premature aging in aneuploid yeast is caused in part by aneuploidy-induced defects in Ribosome Quality Control.bioRxiv : the preprint server for biology · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs.eLife · 2024Article
- Review
- Selective microautophagy of proteasomes is initiated by ESCRT-0 and is promoted by proteasome ubiquitylation.Journal of cell science · 2022Article
- Bro1 binds the Vps20 subunit of ESCRT-III and promotes ESCRT-III regulation by Doa4.Traffic (Copenhagen, Denmark) · 2022Article
- Review
- Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling.International journal of molecular sciences · 2021Article
- Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4.Journal of cell science · 2021Article
- The Ubiquitinated Axon: Local Control of Axon Development and Function by Ubiquitin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Ovarian Tumor Domain-Containing Proteases-Deubiquitylation Enzyme GeneFrontiers in microbiology · 2021Article
- Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- The Cdc48 Complex Alleviates the Cytotoxicity of Misfolded Proteins by Regulating Ubiquitin Homeostasis.Cell reports · 2020Article
- Genetic Selection Based on a Ste6G3 (Bethesda, Md.) · 2020Article
- The putative deubiquitinating enzyme MoUbp4 is required for infection-related morphogenesis and pathogenicity in the rice blast fungus Magnaporthe oryzae.Current genetics · 2020Article
- The ubiquitin hydrolase Doa4 directly binds Snf7 to inhibit recruitment of ESCRT-III remodeling factors inJournal of cell science · 2020Article
- The degradation-promoting roles of deubiquitinases Ubp6 and Ubp3 in cytosolic and ER protein quality control.PloS one · 2020Article
- Arabidopsis ALIX Regulates Stomatal Aperture and Turnover of Abscisic Acid Receptors.The Plant cell · 2019Article
- Targeted Degradation of Glucose Transporters Protects against Arsenic Toxicity.Molecular and cellular biology · 2019Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Attachment of ubiquitin to cellular proteins frequently targets them to the 26S proteasome for degradation. In addition, ubiquitination of cell surface proteins stimulates their endocytosis and eventual degradation in the vacuole or lysosome. In the yeast Saccharomyces cerevisiae, ubiquitin is a long-lived protein, so it must be efficiently recycled from the proteolytic intermediates to which it becomes linked. We identified previously a yeast deubiquitinating enzyme, Doa4, that plays a central role in ubiquitin-dependent proteolysis by the proteasome. Biochemical and genetic data suggest that Doa4 action is closely linked to that of the proteasome. Here we provide evidence that Doa4 is required for recycling ubiquitin from ubiquitinated substrates targeted to the proteasome and, surprisingly, to the vacuole as well. In the doa4Delta mutant, ubiquitin is strongly depleted under certain conditions, most notably as cells approach stationary phase. Ubiquitin depletion precedes a striking loss of cell viability in stationary phase doa4Delta cells. This loss of viability and several other defects of doa4Delta cells are rescued by provision of additional ubiquitin. Ubiquitin becomes depleted in the mutant because it is degraded much more rapidly than in wild-type cells. Aberrant ubiquitin degradation can be partially suppressed by mutation of the proteasome or by inactivation of vacuolar proteolysis or endocytosis. We propose that Doa4 helps recycle ubiquitin from both proteasome-bound ubiquitinated intermediates and membrane proteins destined for destruction in the vacuole.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.