Linked Life Data

20643691

Source:http://linkedlifedata.com/resource/pubmed/id/20643691

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-9-9
pubmed:abstractText
Gaucher disease (GD), a sphingolipidosis characterized by impaired activity of the lysosomal enzyme glucocerebrosidase (GCase), results from mutations in the GCase-encoding gene, GBA. We have shown that mutant GCase variants present variable degrees of endoplasmic reticulum (ER) retention and undergo ER-associated degradation (ERAD) in the proteasome. Furthermore, the degree of ERAD of mutant GCase variants correlates with and is one of the factors that determine GD severity. An association between GD and Parkinson disease (PD) has been demonstrated by the concurrence of PD in GD patients and the identification of GCase mutations in probands with sporadic PD. One of the genes involved in PD is PARK2, encoding the E3 ubiquitin ligase parkin. Parkin functions in the ERAD of misfolded ER proteins, and it is upregulated by unfolded protein response. Loss of parkin function leads to the accumulation of its substrates, which is deleterious to dopaminergic neurons in PD. We, therefore, tested the possibility that the association between GD and PD reflects the fact that parkin acts as an E3 ligase of mutant GCase variants. Our results showed that mutant GCase variants associate with parkin. Normal parkin, but not its RING finger mutants, affects the stability of mutant GCase variants. Parkin also promotes the accumulation of mutant GCase in aggresome-like structures and is involved in K48-mediated polyubiquitination of GCase mutants, indicating its function as its E3 ligase. We suggest that involvement of parkin in the degradation of mutant GCase explains the concurrence of GD and PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3771-81
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher disease.
pubmed:affiliation
Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv 69978, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't