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PMID:23794287
| Citation |
'Tung, YT, Wang, BJ, Hsu, WM, Hu, MK, Her, GM, Huang, WP and Liao, YF (2013) Presenilin-1 Regulates the Expression of p62 to Govern p62-dependent Tau Degradation. Mol. Neurobiol. ' |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1007/s12035-013-8482-y |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0045893: positive regulation of transcription, DNA-dependent |
ECO:0000315: |
P |
In figure 2, it is shown that PS1 mutants in different mouse cells show significantly lower levels of p62 mRNA than in the wild type, indicating that PS1 has a positive effect on the transcription of the p62 gene. |
complete | ||||
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involved_in |
GO:0045893: positive regulation of transcription, DNA-templated |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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