Parkin Is Dispensable for Mitochondrial Function, but Its Ubiquitin Ligase Activity Is Critical for Macroautophagy and Neurotransmitters: Therapeutic Potential beyond Parkinson's Disease

No abstract is available for this paper.

• Publication year

  2015

• Venue

  Neurodegenerative Diseases

• Publication date

  2015-07-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1159/000430888PMID 26160424
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Parkin is activated by PINK 1-dependent phosphorylation of ubiquitin at Ser 65

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• Parkin regulates kainate receptors by interacting with the GluK2 subunit

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• Emerging trends in the epidemiology of melanoma

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• Glioma tumor grade correlates with parkin depletion in mutant p53-linked tumors and results from loss of function of p53 transcriptional activity

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• c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease.

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• Parkin and PINK1: much more than mitophagy.

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• The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy

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• The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy

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• Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65

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• Phosphorylation by PINK1 Releases the UBL Domain and Initializes the Conformational Opening of the E3 Ubiquitin Ligase Parkin

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• Parkin reverses TDP‐43‐induced cell death and failure of amino acid homeostasis

  2014cited by this paper
• Parkin-mediated reduction of nuclear and soluble TDP-43 reverses behavioral decline in symptomatic mice.

  2014cited by this paper
• PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity

  2014cited by this paper
• USP8 regulates mitophagy by removing K6‐linked ubiquitin conjugates from parkin

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• Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin

  2014cited by this paper
• PINK1 triggers autocatalytic activation of Parkin to specify cell fate decisions.

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• Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy

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• Tissue- and Cell-Specific Mitochondrial Defect in Parkin-Deficient Mice

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• PINK1 and Parkin – mitochondrial interplay between phosphorylation and ubiquitylation in Parkinson's disease

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• Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer.

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• Cargo recognition and trafficking in selective autophagy

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• Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance

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• Parkin-catalyzed Ubiquitin-Ester Transfer Is Triggered by PINK1-dependent Phosphorylation*

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• PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding

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• Structure of Parkin Reveals Mechanisms for Ubiquitin Ligase Activation

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• Selective escape of proteins from the mitochondria during mitophagy

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• VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations.

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• The PINK1–Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo

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• Structure of the human Parkin ligase domain in an autoinhibited state

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• Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation

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• Compact Parkin only: insights into the structure of an autoinhibited ubiquitin ligase

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• Parkin Induces Upregulation of 40S Ribosomal Protein SA and Posttranslational Modification of Cytokeratins 8 and 18 in Human Cervical Cancer Cells

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• Parkin mitochondrial translocation is achieved through a novel catalytic activity coupled mechanism

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• Parkin differently regulates presenilin-1 and presenilin-2 functions by direct control of their promoter transcription.

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• Ubiquitination Increases Parkin Activity to Promote Autophagic α-Synuclein Clearance

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• A molecular explanation for the recessive nature of parkin-linked Parkinson’s disease

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• S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson’s disease

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• 100 years of Lewy pathology

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• Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance

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• Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.

  2012cited by this paper
• Parkin prevents cortical atrophy and Aβ-induced alterations of brain metabolism: ¹³C NMR and magnetic resonance imaging studies in AD models.

  2012cited by this paper
• Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs

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• PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65

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• Differential Effects of UCHL1 Modulation on Alpha-Synuclein in PD-Like Models of Alpha-Synucleinopathy

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• Regulation of Parkin E3 ubiquitin ligase activity

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• Contribution of germline mutations to PARK2 gene inactivation in lung adenocarcinoma

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• Parkin Ubiquitinates Tar-DNA Binding Protein-43 (TDP-43) and Promotes Its Cytosolic Accumulation via Interaction with Histone Deacetylase 6 (HDAC6)*

  2012cited by this paper
• Diminished Parkin Solubility and Co-Localization with Intraneuronal Amyloid-β are Associated with Autophagic Defects in Alzheimer's Disease

  2012cited by this paper
• Mutant ataxin-3 promotes the autophagic degradation of parkin

  2011cited by this paper
• Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models.

  2011cited by this paper
• The ubiquitin ligase parkin modulates the execution of autophagy

  2011cited by this paper
• Novel Regulation of Parkin Function through c-Abl-Mediated Tyrosine Phosphorylation: Implications for Parkinson's Disease

  2011cited by this paper
• The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability.

  2011cited by this paper
• Parkin Interacts with Ambra1 to Induce Mitophagy

  2011cited by this paper
• Autoregulation of Parkin activity through its ubiquitin‐like domain

  2011cited by this paper
• UbcH7 reactivity profile reveals Parkin and HHARI to be RING/HECT hybrids

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• The Beclin 1 network regulates autophagy and apoptosis

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• The Beclin 1 interactome.

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• Parkin Enhances the Expression of Cyclin-dependent Kinase 6 and Negatively Regulates the Proliferation of Breast Cancer Cells*

  2010cited by this paper
• Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function

  2010cited by this paper
• PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1

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• The role of parkin in familial and sporadic Parkinson's disease

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• Parkinson's disease: insights from pathways.

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• Parkin promotes intracellular Abeta1-42 clearance.

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• Mitochondrial dysfunction and Parkinson’s disease genes: insights from Drosophila

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• Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases.

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• Parkin as a tumor suppressor gene for hepatocellular carcinoma

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• Pruning and loss of excitatory synapses by the parkin ubiquitin ligase

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• Neurodegenerative lysosomal disorders: A continuum from development to late age

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• alpha-Synuclein aggregates interfere with Parkin solubility and distribution: role in the pathogenesis of Parkinson disease.

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• Tumorigenesis and neurodegeneration: two sides of the same coin?

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• Autophagy fights disease through cellular self-digestion

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• Direct Binding with Histone Deacetylase 6 Mediates the Reversible Recruitment of Parkin to the Centrosome

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• Autophagy in neurodegeneration and development

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• Pathological TDP‐43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations

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• Abl Activation Reduces Parkin Activity and Arrests Autophagy

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• Two sides of the same coin: tyrosine kinase inhibition in cancer and neurodegeneration

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