| http://purl.uniprot.org/citations/18292230 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18292230 | http://www.w3.org/2000/01/rdf-schema#comment | "A hallmark of the pathology of Alzheimer's disease is the accumulation of the microtubule-associated protein tau into fibrillar aggregates. Recent studies suggest that they accumulate because cytosolic chaperones fail to clear abnormally phosphorylated tau, preserving a pool of toxic tau intermediates within the neuron. We describe a mechanism for tau clearance involving a major cellular kinase, Akt. During stress, Akt is ubiquitinated and degraded by the tau ubiquitin ligase CHIP, and this largely depends on the Hsp90 complex. Akt also prevents CHIP-induced tau ubiquitination and its subsequent degradation, either by regulating the Hsp90/CHIP complex directly or by competing as a client protein with tau for binding. Akt levels tightly regulate the expression of CHIP, such that, as Akt levels are suppressed, CHIP levels also decrease, suggesting a potential stress response feedback mechanism between ligase and kinase activity. We also show that Akt and the microtubule affinity-regulating kinase 2 (PAR1/MARK2), a known tau kinase, interact directly. Akt enhances the activity of PAR1 to promote tau hyperphosphorylation at S262/S356, a tau species that is not recognized by the CHIP/Hsp90 complex. Moreover, Akt1 knockout mice have reduced levels of tau phosphorylated at PAR1/MARK2 consensus sites. Hence, Akt serves as a major regulator of tau biology by manipulating both tau kinases and protein quality control, providing a link to several common pathways that have demonstrated dysfunction in Alzheimer's disease."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0709180105"xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Sun M."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Zhang Y.J."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Birnbaum M.J."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Cheng J.Q."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Monks B."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Patterson C."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Leon C."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Morgan D."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Xu Y.F."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Petrucelli L."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Jinwal U.K."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Dickey C.A."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Bailey R.M."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Dunmore J."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Koren J."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/author | "Soresh S."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/pages | "3622-3627"xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/title | "Akt and CHIP coregulate tau degradation through coordinated interactions."xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://purl.uniprot.org/core/volume | "105"xsd:string |
| http://purl.uniprot.org/citations/18292230 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18292230 |