ArticleHuman molecular genetics2009
Combined kinase inhibition modulates parkin inactivation.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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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.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W.Cells · 2024Article
- Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and AMolecules (Basel, Switzerland) · 2023Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.Frontiers in molecular biosciences · 2022Review
- Mitotic HOOK3 phosphorylation by ERK1c drives microtubule-dependent Golgi destabilization and fragmentation.iScience · 2021Article
- The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPPScientific reports · 2020Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.Molecular neurobiology · 2018Review
- Parkinson's disease-associated protein Parkin: an unusual player in cancer.Cancer communications (London, England) · 2018Review
- Phosphorylation of Parkin at serine 131 by p38 MAPK promotes mitochondrial dysfunction and neuronal death in mutant A53T α-synuclein model of Parkinson's disease.Cell death & disease · 2018Article
- Post translational modification of Parkin.Biology direct · 2017Review
- Biomonitorization of iron accumulation in the substantia nigra from Lewy body disease patients.Toxicology reports · 2017Article
- Pathologic and therapeutic implications for the cell biology of parkin.Molecular and cellular neurosciences · 2015Review
- Targeting cyclin-dependent kinases in human cancers: from small molecules to Peptide inhibitors.Cancers · 2015Review
- Parkin Regulation and Neurodegenerative Disorders.Frontiers in aging neuroscience · 2015Review
- RBR E3 ubiquitin ligases: new structures, new insights, new questions.The Biochemical journal · 2014Review
- An emerging role of PARK2 in cancer.Journal of molecular medicine (Berlin, Germany) · 2014Review
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 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the parkin gene cause autosomal-recessive, juvenile-onset parkinsonism, and parkin dysfunction may also play a role in the pathogenesis of sporadic Parkinson disease (PD). Although its precise function remains largely unknown, parkin seems to play a neuroprotective role. Several studies indicate that changes in parkin solubility induced by post-translational modifications, such as S-nitrosylation or dopamine modification, comprise one mechanism of parkin inactivation associated with disease. Protein phosphorylation events have recently been linked to the molecular mechanism(s) underlying PD, but the role of this post-translational modification for parkin function has remained unclear. Here we report that compound phosphorylation of parkin by both casein kinase I and cyclin-dependent kinase 5 (cdk5) decreases parkin solubility, leading to its aggregation and inactivation. Combined kinase inhibition partially reverses the aggregative properties of several pathogenic point mutants in cultured cells. Enhanced parkin phosphorylation is detected in distinct brain areas of individuals with sporadic PD and correlates with increases in the levels of p25, the activator of cdk5. These findings indicate that casein kinase I and cdk5 may represent novel combinatorial therapeutic targets for treating 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.