Linked Life Data

18362144

Source:http://linkedlifedata.com/resource/pubmed/id/18362144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2008-5-12
pubmed:abstractText
Loss-of-function mutations in the Parkin gene (PARK2) are responsible for the majority of autosomal recessive Parkinson disease. A growing body of evidence indicates that misfolding and aggregation of Parkin is a major mechanism of Parkin inactivation, accounting for the loss-of-function phenotype of various pathogenic Parkin mutants. Remarkably, wild-type Parkin is also prone to misfolding under certain cellular conditions, suggesting a more general role of Parkin in the pathogenesis of Parkinson disease. We now show that misfolding of Parkin can lead to two phenotypes: the formation of detergent-insoluble, aggregated Parkin, or destabilization of Parkin resulting in an accelerated proteasomal degradation. By combining two pathogenic Parkin mutations, we could demonstrate that destabilization of Parkin is dominant over the formation of detergent-insoluble Parkin aggregates. Furthermore, a comparative analysis with HHARI, an E3 ubiquitin ligase with an RBR domain highly homologous to that of Parkin, revealed that folding of Parkin is specifically dependent on the integrity of the C-terminal domain, but not on the presence of a putative PDZ-binding motif at the extreme C terminus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13771-9
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation.
pubmed:affiliation
Department of Biochemistry, Neurobiochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Schillerstrasse 44, Munich D-80336, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't