ArticleThe Journal of biological chemistry2016
Interaction between RING1 (R1) and the Ubiquitin-like (UBL) Domains Is Critical for the Regulation of Parkin Activity.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Mitochondrial dysfunction and mitophagy: crucial players in burn trauma and wound healing.Burns & trauma · 2023Review
- Mitophagy in atherosclerosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- Review
- Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation.Human molecular genetics · 2022Article
- Defective PTEN-induced kinase 1/Parkin mediated mitophagy and neurodegenerative diseases.Frontiers in cellular neuroscience · 2022Review
- CVB3-Mediated Mitophagy Plays an Important Role in Viral ReplicationFrontiers in cellular and infection microbiology · 2021Article
- Quantitative Middle-Down MS Analysis of Parkin-Mediated Ubiquitin Chain Assembly.Journal of the American Society for Mass Spectrometry · 2020Article
- PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency.Molecular neurodegeneration · 2020Article
- Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mitochondrial and calcium perturbations in rat CNS neurons induce calpain-cleavage of Parkin: Phosphatase inhibition stabilizes pSerBiochimica et biophysica acta. Molecular basis of disease · 2019Article
- PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy.Cell research · 2018Article
- TMUB1 Inhibits BRL-3A Hepatocyte Proliferation by Interfering with the Binding of CAML to Cyclophilin B through its TM1 Hydrophobic Domain.Scientific reports · 2018Article
- Molecular dynamics simulations of human E3 ubiquitin ligase Parkin.Molecular medicine reports · 2017Article
- Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.Nature structural & molecular biology · 2017Article
- The role of post-translational modifications in hearing and deafness.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkin is an E3 ligase that contains a ubiquitin-like (UBL) domain in the N terminus and an R1-in-between-ring-RING2 motif in the C terminus. We showed that the UBL domain specifically interacts with the R1 domain and negatively regulates Parkin E3 ligase activity, Parkin-dependent mitophagy, and Parkin translocation to the mitochondria. The binding between the UBL domain and the R1 domain was suppressed by carbonyl cyanide m-chlorophenyl hydrazone treatment or by expression of PTEN-induced putative kinase 1 (PINK1), an upstream kinase that phosphorylates Parkin at the Ser-65 residue of the UBL domain. Moreover, we demonstrated that phosphorylation of the UBL domain at Ser-65 prevents its binding to the R1 domain and promotes Parkin activities. We further showed that mitochondrial translocation of Parkin, which depends on phosphorylation at Ser-65, and interaction between the R1 domain and a mitochondrial outer membrane protein, VDAC1, are suppressed by binding of the UBL domain to the R1 domain. Interestingly, Parkin with missense mutations associated with Parkinson disease (PD) in the UBL domain, such as K27N, R33Q, and A46P, did not translocate to the mitochondria and induce E3 ligase activity by m-chlorophenyl hydrazone treatment, which correlated with the interaction between the R1 domain and the UBL domain with those PD mutations. These findings provide a molecular mechanism of how Parkin recruitment to the mitochondria and Parkin activation as an E3 ubiquitin ligase are regulated by PINK1 and explain the previously unknown mechanism of how Parkin mutations in the UBL domain cause PD 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.