Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkin is a ubiquitin-protein isopeptide ligase. It has been suggested that loss of function in parkin causes accumulation and aggregation of its substrates, leading to death of dopaminergic neurons in Parkinson disease. Using the yeast two-hybrid screen, we isolated a RING finger protein that interacted with the N terminus of parkin in a Drosophila cDNA library. Interaction between human parkin and the mammalian RING finger protein homologue Nrdp1/FLRF, a ubiquitin-protein isopeptide ligase that ubiquitinates ErbB3 and ErbB4, was validated by in vitro binding assay, co-immunoprecipitation, and immunofluorescence co-localization. Significantly, pulse-chase experiments showed that cotransfection of Nrdp1 and parkin reduced the half-life of parkin from 5 to 2.5 h. Consistent with these findings, we further observed that degradation of CDCrel-1, a parkin substrate, was facilitated by overexpression of parkin protein. However, co-transfection of Nrdp1 with parkin reversed the effects of parkin on CDCrel-1 degradation. We conclude that Nrdp1 is a parkin modifier that accelerates degradation of parkin, resulting in a reduction of parkin activity.
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PMID:RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity. 1563 91

Changes in yak mitochondria by natural selection in a hypoxic environment could be utilized to understand adaptation to low-oxygen conditions. Therefore, the differences in proteome profile of skeletal muscle mitochondria from yak, dzo, and cattle were analyzed by mass spectrometry, which were then classified into 3 groups, comparing between yak and dzo, yak and cattle, and dzo and cattle. 376 unique mitochondrial proteins were identified, including 192, 191, and 281 proteins in the yak-dzo, yak-cattle, and dzo-cattle groups, respectively. NRDP1 and COQ8A were expressed at higher levels in yak and dzo compared to those in cattle, indicating higher endurance capacity of yak and dzo in a low-oxygen environment. Gene Ontology (GO) terms of biological processes were significantly enriched in oxidation-reduction process, and that of molecular functions and cellular component were enriched in oxidoreductase activity and the mitochondrion, respectively. The most significantly affected pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were Parkinson's disease, Huntington's disease, and oxidative phosphorylation between the yak-cattle and dzo-cattle groups; while metabolic pathways, citrate cycle, and carbon metabolism were significantly affected pathways in the yak-dzo group. ATP synthases, MTHFD1, MDH2, and SDHB were the most enriched hub proteins in the protein-protein interaction (PPI) network. These results indicated that mammals living at high altitudes could possibly possess better bioenergy metabolism than those living in the plains. The key proteins identified in the present study may be exploited as candidate proteins for understanding and fine-tuning mammalian adaptation to high altitudes.
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PMID:Differential expression of skeletal muscle mitochondrial proteins in yak, dzo, and cattle: a proteomics-based study. 3264 22