Linked Life Data

16939621

Source:http://linkedlifedata.com/resource/pubmed/id/16939621

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2006-8-30
pubmed:abstractText
The protein ataxin-3 is responsible for spinocerebellar ataxia type 3, a neurodegenerative disease triggered when the length of a stretch of consecutive glutamines exceeds a critical threshold. Different physiologic roles have been suggested for this protein. More specifically, recent papers have shown that the highly conserved N-terminal Josephin domain of ataxin-3 binds ubiquitin and has ubiquitin hydrolase activity, thanks to a catalytic device specific to cysteine proteases. This article shows that the protein also has autoproteolytic activity, sustained by the same residues responsible for the ubiquitin hydrolase activity. The autolytic activity was abolished when these residues, i.e. Cys14 and His119, were replaced by noncatalytic ones. Furthermore, we found that pretreatment of the protein with tosyl l-phenylalanine chloromethyl ketone also abolished this activity, and that this site-specific reagent covalently bound His119, findings supported by MS experiments. MS also allowed us to establish that the attack was aspecific, as cleavage sites were observed at the carboxyl side of apolar, acidic and polar uncharged residues, clustered in the C-terminal, unstructured domain of the protein. In contrast, the Josephin domain was preserved from attack. We propose that the autolytic activity reported here may play a role in pathogenesis, as fragments carrying expanded polyglutamines are thought to be significantly more toxic than the whole protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1742-464X
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4277-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Ataxin-3 is subject to autolytic cleavage.
pubmed:affiliation
Istituto di Tecnologie Biomediche, CNR, Milano, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't