https://scholars.lib.ntu.edu.tw/handle/123456789/469994
標題: | Presenilin-1 regulates the expression of p62 to govern p62-dependent tau degradation | 作者: | Tung Y.-T. Wang B.-J. WEN-MING HSU Hu M.-K. Her G.M. Huang W.-P. Liao Y.-F. |
公開日期: | 2014 | 出版社: | Humana Press Inc. | 卷: | 49 | 期: | 1 | 起(迄)頁: | 10-27 | 來源出版物: | Molecular Neurobiology | 摘要: | Mutations in presenilin-1 (PS1) are tightly associated with early-onset familial Alzheimer's disease (FAD), which is characterized by extracellular amyloid plaques and the accumulation of intracellular Tau. In addition to being the catalytic subunit of γ-secretase, PS1 has been shown to regulate diverse cellular functions independent of its proteolytic activity. We found that cells deficient in PS1 exhibit reduced levels of p62 protein, a cargo-receptor shuttling Tau for degradation. The downregulation of PS1 led to a significant decrease in both the protein and mRNA transcript of p62, concomitant with attenuated p62 promoter activity. This PS1-dependent regulation of p62 expression was mediated through an Akt/AP-1 pathway independent of the proteolytic activity of PS1/γ-secretase. This p62-mediated Tau degradation was significantly impaired in PS1-deficient cells, which can be rescued by ectopic expression of either p62 or wild-type PS1 but not mutant PS1 containing FAD-linked mutations. Our study suggests a novel function for PS1 in modulating p62 expression to control the proteostasis of Tau. ? 2013 Springer Science+Business Media New York. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84894364673&doi=10.1007%2fs12035-013-8482-y&partnerID=40&md5=e2adb4c7f03ecbdd86f5f7d9888bf2fe https://scholars.lib.ntu.edu.tw/handle/123456789/469994 |
ISSN: | 0893-7648 | DOI: | 10.1007/s12035-013-8482-y | SDG/關鍵字: | gamma secretase; messenger RNA; presenilin 1; protein kinase B; protein p62; tau protein; transcription factor AP 1; Alzheimer disease; amyloid plaque; animal cell; cell function; controlled study; enzyme active site; gene mutation; genetic transcription; human; human cell; molecular biology; mouse; nonhuman; protein degradation; protein expression; protein homeostasis; review; Animals; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation; HEK293 Cells; Humans; Mice; Mice, Knockout; Mutation; Phenotype; Presenilin-1; Proteolysis; RNA-Binding Proteins; tau Proteins; Zebrafish |
顯示於: | 醫學系 |
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