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http://purl.uniprot.org/citations/16443603http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16443603http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16443603http://www.w3.org/2000/01/rdf-schema#comment"One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of paired helical filaments (PHFs) of hyperphosphorylated microtubule-associated protein Tau. Tandem mass spectrometry was employed to examine PHF-Tau post-translational modifications, in particular protein phosphorylation and ubiquitination, to shed light on their role in the early stages of Alzheimer disease. PHF-Tau from Alzheimer disease brain was affinity-purified by MC1 monoclonal antibody to isolate a soluble fraction of PHF-Tau in a conformation unique to human AD brain. A large number of phosphorylation sites were identified by employing a data-dependent neutral loss algorithm to trigger MS3 scans of phosphopeptides. It was found that soluble PHF-Tau is ubiquitinated at its microtubule-binding domain at residues Lys-254, Lys-311, and Lys-353, suggesting that ubiquitination of PHF-Tau may be an earlier pathological event than previously thought and that ubiquitination could play a regulatory role in modulating the integrity of microtubules during the course of AD. Tandem mass spectrometry data for ubiquitin itself indicate that PHF-Tau is modified by three polyubiquitin linkages, at Lys-6, Lys-11, and Lys-48. Relative quantitative analysis indicates that Lys-48-linked polyubiquitination is the primary form of polyubiquitination with a minor portion of ubiquitin linked at Lys-6 and Lys-11. Because modification by Lys-48-linked polyubiquitin chains is known to serve as the essential means of targeting proteins for degradation by the ubiquitin-proteasome system, and it has been reported that modification at Lys-6 inhibits ubiquitin-dependent protein degradation, a failure of the ubiquitin-proteasome system could play a role in initiating the formation of degradation-resistant PHF tangles."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m512786200"xsd:string
http://purl.uniprot.org/citations/16443603http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m512786200"xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Davies P."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Davies P."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Yang F."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Yang F."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Yang A.J."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Yang A.J."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Cripps D."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Cripps D."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Jeng Y."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Jeng Y."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Thomas S.N."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/author"Thomas S.N."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/pages"10825-10838"xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/pages"10825-10838"xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/title"Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation."xsd:string
http://purl.uniprot.org/citations/16443603http://purl.uniprot.org/core/title"Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation."xsd:string
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