ArticlePloS one2010
Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 64 citations in OpenAlex.
- The EF-hand domain of MINDY3 is a ubiquitin and RAD23 UBL-binding domain.EMBO reports · 2026Article
- Polyglutamine-Expanded Ataxin-3 Accelerates CFTR Degradation Through K63-Linked Ubiquitination to Exacerbate Microglial Inflammation.ASN neuro · 2026Article
- Ubiquitin Azapeptide Esters as Next-Generation Activity-Based Probes for Cysteine Enzymes in the Ubiquitin Signal Pathway.Journal of the American Chemical Society · 2025Article
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases.The Biochemical journal · 2024Review
- Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.Frontiers in molecular neuroscience · 2023Article
- Regional and age-dependent changes in ubiquitination in cellular and mouse models of spinocerebellar ataxia type 3.Frontiers in molecular neuroscience · 2023Article
- Article
- Article
- Glutamatergic Synapse Dysfunction inFrontiers in molecular neuroscience · 2022Article
- Ubiquitin-binding site 1 of pathogenic ataxin-3 regulates its toxicity inFrontiers in neuroscience · 2022Article
- Targeting the VCP-binding motif of ataxin-3 improves phenotypes in Drosophila models of Spinocerebellar Ataxia Type 3.Neurobiology of disease · 2021Article
- Article
- The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy.Aging cell · 2020Article
- Expression and Regulation of Deubiquitinase-Resistant, Unanchored Ubiquitin Chains in Drosophila.Scientific reports · 2018Article
- Destabilizing the AXH Tetramer by Mutations: Mechanisms and Potential Antiaggregation Strategies.Biophysical journal · 2018Article
- Antisense Oligonucleotide-Mediated Removal of the Polyglutamine Repeat in Spinocerebellar Ataxia Type 3 Mice.Molecular therapy. Nucleic acids · 2017Article
- Ataxin-3 promotes genome integrity by stabilizing Chk1.Nucleic acids research · 2017Article
- Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.Human molecular genetics · 2017Article
- Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch.Frontiers in neuroscience · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Ataxin-3, the disease protein in the neurodegenerative disorder Spinocerebellar Ataxia Type 3 or Machado Joseph disease, is a cysteine protease implicated in the ubiquitin proteasome pathway. It contains multiple ubiquitin binding sites through which it anchors polyubiquitin chains of different linkages that are then cleaved by the N-terminal catalytic (Josephin) domain. The properties of the ubiquitin interacting motifs (UIMs) in the C-terminus of ataxin-3 are well established. Very little is known, however, about how two recently identified ubiquitin-binding sites in the Josephin domain contribute to ubiquitin chain binding and cleavage. In the current study, we sought to define the specific contribution of the Josephin domain to the catalytic properties of ataxin-3 and assess how the topology and affinity of these binding sites modulate ataxin-3 activity. Using NMR we modeled the structure of diUb/Josephin complexes and showed that linkage preferences are imposed by the topology of the two binding sites. Enzymatic studies further helped us to determine a precise hierarchy between the sites. We establish that the structure of Josephin dictates specificity for K48-linked chains. Site 1, which is close to the active site, is indispensable for cleavage. Our studies open the way to understand better the cellular function of ataxin-3 and its link to pathology.
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.