ArticlePloS one2012
Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Review
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- The ARTS of p53-dependent mitochondrial apoptosis.Journal of molecular cell biology · 2023Review
- Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy.Circulation research · 2023Article
- Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Peiminine Reduces ARTS-Mediated Degradation of XIAP by Modulating the PINK1/Parkin Pathway to Ameliorate 6-Hydroxydopamine Toxicity and α-Synuclein Accumulation in Parkinson's Disease Models In Vivo and In Vitro.International journal of molecular sciences · 2021Article
- p53 induces ARTS to promote mitochondrial apoptosis.Cell death & disease · 2021Article
- Modulation of ARTS and XIAP by Parkin Is Associated with Carnosic Acid Protects SH-SY5Y Cells against 6-Hydroxydopamine-Induced Apoptosis.Molecular neurobiology · 2018Article
- Construction of a recombinant pIRES2-EGFP-ARTS plasmid and its effect on LX-2 cells.Molecular medicine reports · 2017Article
- Gene therapy targeting mitochondrial pathway in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2017Review
- PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis.International journal of molecular sciences · 2017Review
- Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.PloS one · 2016Article
- Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.PloS one · 2015Article
- Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin.Cell death & disease · 2014Article
- Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition with its substrates PARIS and ARTS.Orphanet journal of rare diseases · 2014Article
- RBR E3 ubiquitin ligases: new structures, new insights, new questions.The Biochemical journal · 2014Review
- Unfolded protein response in Gaucher disease: from human to Drosophila.Orphanet journal of rare diseases · 2013Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is associated with excessive cell death causing selective loss of dopaminergic neurons. Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD. ARTS (Sept4_i2) is a mitochondrial protein, which initiates caspase activation upstream of cytochrome c release in the mitochondrial apoptotic pathway. Here we show that Parkin serves as an E3-ubiquitin ligase to restrict the levels of ARTS through UPS-mediated degradation. Though Parkin binds equally to ARTS and Sept4_i1 (H5/PNUTL2), the non-apoptotic splice variant of Sept4, Parkin ubiquitinates and degrades only ARTS. Thus, the effect of Parkin on ARTS is specific and probably related to its pro-apoptotic function. High levels of ARTS are sufficient to promote apoptosis in cultured neuronal cells, and rat brains treated with 6-OHDA reveal high levels of ARTS. However, over-expression of Parkin can protect cells from ARTS-induced apoptosis. Furthermore, Parkin loss-of-function experiments reveal that reduction of Parkin causes increased levels of ARTS and apoptosis. We propose that in brain cells in which the E3-ligase activity of Parkin is compromised, ARTS levels increase and facilitate apoptosis. Thus, ARTS is a novel substrate of Parkin. These observations link Parkin directly to a pro-apoptotic protein and reveal a novel connection between Parkin, apoptosis, and PD.
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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.