RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity
Document Type
Journal ArticlePublication Date
2005-01-06Keywords
AnimalsDrosophila
Drosophila Proteins
Humans
Kinetics
Polymerase Chain Reaction
Proteins
Ubiquitin-Protein Ligases
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2005 Mar 11;280(10):9425-30. Epub 2005 Jan 4. Link to article on publisher's siteDOI
10.1074/jbc.M408955200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42340PubMed ID
15632191Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M408955200