Linked Life Data

16186628

Source:http://linkedlifedata.com/resource/pubmed/id/16186628

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-9-27
pubmed:abstractText
The ubiquitin-proteasome pathway (UPP) has been implicated in the regulation of a number of key cellular processes in mammalian cells, including the cell cycle and apoptosis. Furthermore, defects in the UPP have been implicated in neurodegenerative disorders such as Parkinson's disease (PD), as mutations in the ubiquitin ligase Parkin underlie a familial form of parkinsonism and ubiquitinated inclusions are a defining hallmark of PD pathology. To functionally dissect molecular components of the UPP in postmitotic neurons, we used RNA interference to knock down genes that encode genetically characterized components of the UPP. Here, we show that knockdown of two such components, the ubiquitin ligase scaffolding protein Cullin-1 (Cul-1) and the proteasome-associated deubiquitinating protein Pad-1, lead to cell cycle reactivation and apoptosis in subsets of postmitotic neurons. Furthermore, knockdown of Cul-1 appears to specifically affect the dopaminergic population. These data support the hypothesis that the UPP normally functions to regulate cell-cycle reentry in postmitotic neurons and further implicate this pathway in dopamine neuron degeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0895-8696
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
The ubiquitin-proteasome pathway is necessary for maintenance of the postmitotic status of neurons.
pubmed:affiliation
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural