Linked Life Data

19345187

Source:http://linkedlifedata.com/resource/pubmed/id/19345187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-4-6
pubmed:abstractText
Huntington's disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in HD. We report here that such clearance can be achieved by posttranslational modification of the mutant Huntingtin (Htt) by acetylation at lysine residue 444 (K444). Increased acetylation at K444 facilitates trafficking of mutant Htt into autophagosomes, significantly improves clearance of the mutant protein by macroautophagy, and reverses the toxic effects of mutant huntingtin in primary striatal and cortical neurons and in a transgenic C. elegans model of HD. In contrast, mutant Htt that is rendered resistant to acetylation dramatically accumulates and leads to neurodegeneration in cultured neurons and in mouse brain. These studies identify acetylation as a mechanism for removing accumulated protein in HD, and more broadly for actively targeting proteins for degradation by autophagy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4172
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
60-72
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Acetylation targets mutant huntingtin to autophagosomes for degradation.
pubmed:affiliation
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural