The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway
Open accessAbstract
Conditional mouse models of polyglutamine diseases, such as Huntington's disease (HD), have revealed that cells can clear accumulated pathogenic proteins if the continuous production of the mutant transgene is halted. Invariably, the clearance of the protein leads to regression of the disease symptoms in mice. In light of these findings, it is critical to determine the pathway responsible for alleviating this protein accumulation to define targets to fight these diseases. In a functional genetic screen of HD, we found that activation of insulin receptor substrate-2, which mediates the signaling cascades of insulin and insulin-like growth factor 1, leads to a macroautophagy-mediated clearance of the accumulated proteins. The macroautophagy is triggered despite activation of Akt, mammalian target of rapamycin (mTOR), and S6 kinase, but still requires proteins previously implicated in macroautophagy, such as Beclin1 and hVps34. These findings indicate that the accumulation of mutant protein can lead to mTOR-independent macroautophagy and that lysosome-mediated degradation of accumulated protein differs from degradation under conditions of starvation.
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Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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“Antibodies were purchased from Upstate Biotechnology (anti–IRS-2, anti–phospho Akt, and anti–phospho S6 kinase), BD Biosciences (Akt, S6 kinase, and IRS-1), Cell Signaling Technology (anti–phospho-mTOR and anti-mTOR), and Roche (anti-GFP). htt-exon1 (CAGCAA) constructs were obtained from A. Kazantsev (Massachusets Gen…”
BackgroundInfluentialHDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin.
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Cited by
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
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Self-citationFoxO3 Controls Autophagy in Skeletal Muscle In Vivo
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Metadata
- Authors
- Yamamoto, A., Cremona, M. L., & Rothman, J. E.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2006-02-27
- Volume
- 172
- Issue
- 5
- Pages
- 719-731
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2154404753
- Cited by
- 360
- References
- 11
- FWCI
- 11.34
- Type
- journal article
- Language
- en
- Open access
- green
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