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PMID:18541373

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Citation

Yu, F and Zhou, J (2008) Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress. Neurosci. Lett. 440:4-8

Abstract

Parkin plays an important role in the pathogenesis of Parkinson's disease. We previously described that Nrdp1, a RING-finger ubiquitin E3 ligase, interacted with Parkin by the yeast two-hybrid assay and by co-immunoprecipitation. Here we further demonstrated that overexpression of Nrdp1 significantly reduced the endogenous Parkin level in an Nrdp1 dosage-dependent and proteasome-dependent manner. More importantly, Nrdp1 ubiquitinated Parkin and catalyzed the poly-ubiquitin chains on Parkin in vitro as well as in cells, indicating Parkin is an Nrdp1 substrate. In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. Conversely, suppression of Nrdp1 by shRNA conferred SH-SY5Y cells a lower ROS level. Together, we provided evidence that interactions between Nrdp1 and Parkin negatively regulated Parkin level and affected ROS production, suggesting that Nrdp1 may play a role in Parkinson's disease.

Links

PubMed Online version:10.1016/j.neulet.2008.05.052

Keywords

Cell Line; Dose-Response Relationship, Drug; Gene Expression Regulation/drug effects; Humans; Immunoprecipitation/methods; Mutation/physiology; Oxidative Stress/drug effects; Oxidative Stress/physiology; RNA, Small Interfering/pharmacology; Reactive Oxygen Species/metabolism; Transfection/methods; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; Ubiquitin-Protein Ligases/pharmacology; Ubiquitin-Protein Ligases/physiology; Ubiquitination/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PRKN

involved_in

GO:2000378: negative regulation of reactive oxygen species metabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9H4P4

P

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN

involved_in

GO:2000377: regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNF41

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:O60260)

Seeded From UniProt

complete

HUMAN:RNF41

involved_in

GO:0010498: proteasomal protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:O60260)

Seeded From UniProt

complete

HUMAN:RNF41

involved_in

GO:2000379: positive regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNF41

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O60260)

Seeded From UniProt

complete

HUMAN:RNF41

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNF41

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:RNF41

involved_in

GO:2000377: regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:2000378: negative regulation of reactive oxygen species metabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9H4P4

P

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:2000377: regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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