anti-Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) Antibodies

Fruit Fly (Drosophila melanogaster) Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) interaction partners

1. this study show that parkin deficient astrocytes have an exaggerated ER stress signature, increased JNK activation and blunting of neurotropic factor transcript induction following ER stress.

2. The reduced expression of Parkin and HtrA2 interpret defective mitophagy leading to clustering of fragmented mitochondria and apoptotic inhibition in scrib knockdown tumors.

3. Parkin null mutation is associated with climbing defects and defects and mitochondrial activity.

4. Loss of parkin is associated with nuclear clustering and morphology defects in larval muscles and thus developing aortic aneurysms.

5. This study found learning and memory abnormalities in Parkin mutant genotypes in Drosophila.

6. parkin mutants have a longer lifespan when fed the 1:16 P:C compared to those fed the 1:2 P:C diet. Parkin mutants fed the 1:16 P:C diet have delayed climbing deficit, increased resistance to starvation. Mutant flies fed the 1:16 P:C diet also have improved mitochondrial functions as evidenced by increased respiratory control ratio

7. Drosophila CHIP protects against mitochondrial dysfunction by acting downstream of Pink1 in parallel with Parkin

8. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced intestinal stem cell proliferation, in part, through induction of ISC senescence.

9. activation of endoplasmic reticulum stress by defective mitochondria is neurotoxic in pink1 and parkin flies and that the reduction of this signalling is neuroprotective, independently of defective mitochondria.

10. Pharmacological or genetic activation of heat shock protein 70 (Hsp70) protects against loss of parkin Function. Heat shock protein members may act as compensatory factors for parkin loss of function and that the exploitation of these factors may be of potential therapeutic value.

11. autophosphorylation of PINK1 is essential for the mitochondrial translocation of Parkin and for subsequent phosphorylation and activation of Parkin.

12. Our data indicate that PINK1 and Parkin play an important role in FUS-induced neurodegeneration. This study has uncovered a previously unknown link between FUS proteinopathy and PINK1/Parkin genes, providing new insights into the pathogenesis of FUS proteinopathy.

13. Clu is upstream of and binds to VCP in vivo and promotes VCP-dependent Marf degradation in vitro Marf accumulates in whole muscle lysates of clu-deficient flies and is destabilized upon Clu overexpression. Thus, Clu is essential for mitochondrial homeostasis and functions in concert with Parkin and VCP for Marf degradation to promote damaged mitochondrial clearance.

14. Buffy has a role enhancing the loss of parkin and suppressing the loss of Pink1 phenotypes in Drosophila

15. Parkin-dependent mitophagy suppresses neural neurodegeneration by removing damaged mitochondria.

16. We demonstrate here that vps35 genetically interacts with parkin

17. Clu directly modulates mitochondrial function, and that Clu's function contributes to the PINK1-Park pathway of mitochondrial quality control.

18. Human Mask homolog ANKHD1 may serve as a potential therapeutic target for treating Parkinson disease caused by pink1/parkin mutations.

19. These results indicate that the in vivo rescue is due to restoring CI activity rather than promoting mitophagy Our findings support the emerging view that PINK1 plays a role in regulating CI activity separate from its role with Parkin in mitophagy

20. MUL1 acts in parallel to the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity.

Human Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) interaction partners

1. Single nucleotide polymorphism in PARK2 gene is associated with schizophrenia.

2. Parkin is an ubiquitin E3 ligase, and plays important roles in a variety of cellular processes implicated in tumorigenesis, including cell cycle, cell proliferation, apoptosis, metastasis, mitophagy and metabolic reprogramming [Review].

3. The results show that novel compound heterozygous mutations were identified in a Chinese pedigree that might represent a cause of familial EOPD with autosomal dominant inheritance.

4. MIDN promotes the expression of parkin E3 ubiquitin ligase, and that MIDN loss can trigger Parkinson's disease-related pathogenic mechanisms.

5. Define the kinetics and site specificity of PARKIN-dependent target ubiquitylation, and mechanistically define the role of PARKIN UBL phosphorylation in pathway activation in induced neurons.

6. The findings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity.

7. data show how autoinhibition in parkin is resolved, and suggest a mechanism for how parkin ubiquitinates its substrates via an untethered RING2 domain; these findings open new avenues for the design of parkin activators for clinical use

8. Five different PRKN structural variations were identified in families with early onset Parkinson disease. All identified PRKN SVs might originate through retrotransposition events.

9. work provides a framework for the mechanisms of parkin's loss-of-function, indicating an interplay between ARJP-associated substitutions and phosphorylation of its Ubl domain.

10. Data show that E3 ubiquitin-protein ligase parkin (Parkin) undergoes a conformational change upon phosphorylation.

11. carnosic acid induces parkin by enhancing the ubiquitination of ARTS, leading to induction of XIAP.

12. PARK2 promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated with the risk of colorectal cancer development

13. Increased levels of Parkin are detected in lens epithelial cells exposed to H2O2-oxidative stress. Parkin translocates to mitochondria of lens epithelial cells upon H2O2-oxidative stress exposure. Parkin ubiquitin ligase activity is required for clearance of damaged mitochondria in lens epithelial cells exposed to H2O2-oxidative stress.

14. Examined the enzymatic activity of Parkin with M458L mutation. We show that the M458L mutant retains its autoubiquitination potential in vitro but not in cells. M458L mutant fails to protect the mitochondria against hydrogen peroxide, leading to cell death.

15. The results demonstrate that Nix can serve as an alternative mediator of mitophagy to maintain mitochondrial turnover, identifying Nix as a promising target for neuroprotective treatment in PINK1/Parkin-related Parkinson's disease.

16. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence

17. Studies indicate a functional PTEN-induced putative kinase 1)(PINK1)/E3 ubiquitin protein ligase (parkin) mitophagy pathway in neurons [Review].

18. indings indicate that PRKN mutations are associated with large global gene expression changes as observed in fibroblasts from PRKN-Parkinson's disease patients

19. parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neuron

20. Parkin expression is inversely correlated with HIF-1alpha expression and metastasis in breast cancer. Results reveal an important mechanism for Parkin in tumor suppression and HIF-1alpha regulation.

Zebrafish Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) interaction partners

1. Melatonin, added together with MPTP or added once MPTP was removed, prevented and recovered, respectively, the parkinsonian phenotype once it was established, restoring gene expression and normal function of the parkin/PINK1/DJ-1/MUL1 loop and also the normal motor activity of the embryos.

Pig (Porcine) Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) interaction partners

1. Single nucleotide polymorphism (SNP) analysis revealed seven SNPs in the porcine PARK2 gene, one missense and one silent mutation in exon 7 and five SNPs in intron 7

Mouse (Murine) Parkinson Protein 2, E3 Ubiquitin Protein Ligase (Parkin) (PARK2) interaction partners

1. Parkin gene defect did not increase the susceptibility of neonatal mice to adverse health effects associated with high-dose manganese exposure.

2. Parkin gene silencing in primary cortical neurons selectively disrupts the vesicular sorting of the autophagy receptor ATG9A, a WASH-dependent retromer cargo. Parkin is not required for dopaminergic neurodegeneration induced by the expression of PD-linked D620N VPS35 in mice, consistent with VPS35 being located downstream of parkin function

3. Phenotypically, Parkin (S65A/S65A) mice exhibit selective motor dysfunction in the absence of any overt neurodegeneration or alterations in nigrostriatal mitophagy.

4. Low parkin expression is associated with Parkinson's disease.

5. Parkin functions to blunt excessive CHOP to prevent maladaptive ER stress-induced cell death and adverse cardiac ventricular remodeling.

6. data suggested that suppressed Sirt3-Foxo3A-Parkin signaling mediated downregulation of mitophagy may play a vital role in the development of diabetic cardiomyopathy.

7. Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRalpha (a regulator of eNOS) protein and the enhancement of ERRalpha ubiquitination.

8. Parkin mice carrying a deletion in exon 3 display impairments in the main pathway responsible for maintaining BH4 levels in the CNS, an essential cofactor for dopamine synthesis, under inflammatory conditions. Concomitant to this alteration, striatum cells do not upregulate BDNF to confer neuroprotection in LPS-exposed mice, displaying an increased number of mitochondria of smaller size with perinuclear clustering.

9. the results indicate that PICK1 is a potent inhibitor of Parkin, and the reduction of PICK1 enhances the protective effect of Parkin.

10. PINK1 and PARK2 suppress pancreatic tumorigenesis through control of mitochondrial iron-mediated immunometabolism

11. When fed with iron-supplemented diet, DMT1-expressing mice exhibit rather selective accumulation of iron in the substantia nigra but otherwise seem normal. Parkin expression is also enhanced, likely as a neuroprotective response. When DMT1 is overexpressed against a Parkin null background, the double-mutant mice similarly resisted a disease phenotype when fed with iron or manganese, but greater susceptibility to 6-OHDA.

12. Bnip3l knockout (bnip3l(-/-)) impaired mitophagy and aggravated cerebral I-R (ischemia-reperfusion) injury in mice, which can be rescued by BNIP3L overexpression. The rescuing effects of BNIP3L overexpression can be observed in park2(-/-) mice, which showed mitophagy deficiency after I-R.

13. Parkin acts as a regulator of microtubule system during neuronal aging.

14. The expression of PINK1 and Parkin were elevated in white adipose tissue in obese mice.

15. crossed Parkin knockouts to the Twinkle-TG mouse in which mtDNA deletions are increased specifically in substantia nigra to determine the effect of increased deletion mutagenesis in the absence of mitochondrial quality control

16. These findings reveal parkin-mediated cytoprotective mechanisms against misfolded SOD1 toxicity.

17. Park2 deficiency exacerbates ethanol-induced dopaminergic neuron damage through p38 kinase dependent inhibition of autophagy and mitochondrial function.

18. PARK2-dependent acidic postconditioning -induced mitophagy renders the brain resistant to ischemic injury.

19. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process.

20. an impaired PINK1-PARK2-mediated neuroimmunology pathway contributes to septic death.