ArticleProceedings of the National Academy of Sciences of the United States of America2018
PICK1 inhibits the E3 ubiquitin ligase activity of Parkin and reduces its neuronal protective effect.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Phytogenic Nanoparticles for Parkinson's Disease Therapy: Mechanistic Insights, Brain-Targeted Delivery and Neuroprotective Potential.Molecular neurobiology · 2026Review
- Protein interacting with C-kinase 1 (PICK1) regulates synaptic function and reversal learning in a mouse model for schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- PICK1 links KIBRA and AMPA receptor subunit GluA2 in coiled-coil-driven supramolecular complexes.The Journal of biological chemistry · 2025Article
- Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation.Molecular biology of the cell · 2024Article
- FOXO3a-dependent PARKIN negatively regulates cardiac hypertrophy by restoring mitophagy.Cell & bioscience · 2022Article
- A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.EMBO molecular medicine · 2020Article
- Nuclear Parkin Activates the ERRα Transcriptional Program and Drives Widespread Changes in Gene Expression Following Hypoxia.Scientific reports · 2020Article
- Article
- Residue-Level Contact Reveals Modular Domain Interactions of PICK1 Are Driven by Both Electrostatic and Hydrophobic Forces.Frontiers in molecular biosciences · 2020Article
- Cellular and pathophysiological consequences of Arp2/3 complex inhibition: role of inhibitory proteins and pharmacological compounds.Cellular and molecular life sciences : CMLS · 2019Review
- Phosphoregulation on mitochondria: Integration of cell and organelle responses.CNS neuroscience & therapeutics · 2019Review
- Predicting Parkinson's Disease Genes Based on Node2vec and Autoencoder.Frontiers in genetics · 2019Article
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
Parkin functions as a multipurpose E3 ubiquitin ligase, and Parkin loss of function is associated with both sporadic and familial Parkinson's disease (PD). We report that the Bin/Amphiphysin/Rvs (BAR) domain of protein interacting with PRKCA1 (PICK1) bound to the really interesting new gene 1 (RING1) domain of Parkin and potently inhibited the E3 ligase activity of Parkin by disrupting its interaction with UbcH7. Parkin translocated to damaged mitochondria and led to their degradation in neurons, whereas PICK1 robustly inhibited this process. PICK1 also impaired the protective function of Parkin against stresses in SH-SY5Y cells and neurons. The protein levels of several Parkin substrates were reduced in young PICK1-knockout mice, and these mice were resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated toxicity. Taken together, the results indicate that PICK1 is a potent inhibitor of Parkin, and the reduction of PICK1 enhances the protective effect of Parkin.
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