ArticlePLoS biology2016
The Machado-Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- JOSD1-mediated stabilization of SUFU controls pancreatic cancer progression.Cell death & disease · 2026Article
- TgJosephin and TgRad23 are important for anti-IFN-γ virulence via deubiquitination of SPM1 inmSphere · 2026Article
- Review
- The role of deubiquitinase USP33 in colorectal cancer tumorigenesis and its potential as a therapeutic target predictor.Discover oncology · 2026Review
- Repurposing of natural products for spinocerebellar ataxia type 3 using integrated network pharmacology and in silico approaches.Scientific reports · 2026Article
- Hypoxia promotes progression of cervical cancer by modulating the ATXN3-enhanced P53 stability or STAT5 phosphorylation.Cell death discovery · 2026Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- The deubiquitinating enzyme ATXN3 promotes hepatocellular carcinoma progression by stabilizing TAZ.Cancer gene therapy · 2025Article
- Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum.Cellular and molecular life sciences : CMLS · 2024Review
- 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
- Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8International journal of molecular sciences · 2023Article
- miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.Cell death discovery · 2023Article
- ER CaCell & bioscience · 2023Article
- ATXN3 controls DNA replication and transcription by regulating chromatin structure.Nucleic acids research · 2023Article
- ATXN3 promotes prostate cancer progression by stabilizing YAP.Cell communication and signaling : CCS · 2023Article
- Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a deubiquitinating enzyme (DUB), the physiological substrates of ataxin-3 (ATX-3) remain elusive, which limits our understanding of its normal cellular function and that of pathogenic mechanism of spinocerebellar ataxia type 3 (SCA3). Here, we identify p53 to be a novel substrate of ATX-3. ATX-3 binds to native and polyubiquitinated p53 and deubiquitinates and stabilizes p53 by repressing its degradation through the ubiquitin (Ub)-proteasome pathway. ATX-3 deletion destabilizes p53, resulting in deficiency of p53 activity and functions, whereas ectopic expression of ATX-3 induces selective transcription/expression of p53 target genes and promotes p53-dependent apoptosis in both mammalian cells and the central nervous system of zebrafish. Furthermore, the polyglutamine (polyQ)-expanded ATX-3 retains enhanced interaction and deubiquitination catalytic activity to p53 and causes more severe p53-dependent neurodegeneration in zebrafish brains and in the substantia nigra pars compacta (SNpc) or striatum of a transgenic SCA3 mouse model. Our findings identify a novel molecular link between ATX-3 and p53-mediated cell death and provide an explanation for the direct involvement of p53 in SCA3 disease pathogenesis.
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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.