『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
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審査 (推奨):
カテゴリ (推奨):
共著種別 (推奨):
学究種別 (推奨):
組織 (推奨):
著者 (必須): 1. (英) Dunys Julie (日) (読)
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2.瓦井 俊孝
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3. (英) Wilk Sherwin (日) (読)
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4. (英) St George-Hyslop Peter (日) (読)
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5. (英) Alves da Costa Cristine (日) (読)
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6. (英) Checler Frédéric (日) (読)
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題名 (必須): (英) Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins.  (日)    [継承]
副題 (任意):
要約 (任意): (英) PS (presenilin)-dependent gamma-secretase occurs as a high-molecular-mass complex composed of either PS1 or PS2 associated with Nct (nicastrin), PEN2 (presenilin enhancer 2 homologue) and APH1 (anterior pharynx defective 1 homologue). Numerous reports have documented the very complicated physical and functional cross-talk between these proteins that ultimately governs the biological activity of the gamma-secretase, but very few studies examined the fate of the components of the complex. We show that, in both HEK-293 cells and the TSM1 neuronal cell line, the immunoreactivities of overexpressed myc-tagged-APH1a and -PEN2 were enhanced by the proteasome inhibitors ZIE and lactacystin, whereas a broad range of protease inhibitors had no effect. By contrast, proteasome inhibitors were totally unable to affect the cellular expression of endogenous APH1aL and PEN2 in HEK-293 cells, TSM1 and primary cultured cortical neurons. To explain this apparent discrepancy, we examined the degradation of myc-tagged-APH1a and -PEN2, in vitro, by cell extracts containing endogenous proteasome and by purified 20S proteasome. Strikingly, myc-tagged-APH1a and -PEN2 resist proteolysis by endogenous proteasome and purified 20S proteasome. We also show that endogenous PEN2 expression was drastically higher in wild-type than in PS- and Nct-deficient fibroblasts and was enhanced by proteasome inhibitors only in the two deficient cell systems. However, here again, purified 20S proteasome appeared unable to cleave endogenous PEN2 present in PS-deficient fibroblasts. The levels of endogenous APH1aL-like immunoreactivity were not modified by proteasome inhibitors and were unaffected by PS deficiency. Altogether, our results indicate that endogenous PEN2 and APH1aL do not undergo proteasomal degradation under physiological conditions in HEK-293 cells, TSM1 cells and fibroblasts and that the clearance of PEN2 in PS- and Nct-deficient fibroblasts is not mediated by 20S proteasome. Whether the 26S proteasome participates to PEN2 proteolysis in deficient fibroblasts remains to be established.  (日)    [継承]
キーワード (推奨): 1. (英) Animals (日) (読) [継承]
2. (英) Cattle (日) (読) [継承]
3. (英) Cell Line (日) (読) [継承]
4. (英) Endopeptidases (日) (読) [継承]
5. (英) Fibroblasts (日) (読) [継承]
6. (英) Gene Deletion (日) (読) [継承]
7. (英) Gene Expression (日) (読) [継承]
8. (英) Humans (日) (読) [継承]
9. (英) Membrane Proteins (日) (読) [継承]
10. (英) Mice (日) (読) [継承]
11. (英) Neurons (日) (読) [継承]
12. (英) Proteasome Endopeptidase Complex (日) (読) [継承]
13. (英) Proteasome Inhibitors (日) (読) [継承]
14. (英) Proteins (日) (読) [継承]
15. (英) Receptors, Notch (日) (読) [継承]
16. (英) Transfection (日) (読) [継承]
発行所 (推奨):
誌名 (必須): The Biochemical Journal ([The Biochemical Society])
(pISSN: 0264-6021, eISSN: 1470-8728)

ISSN (任意): 1470-8728
ISSN: 0264-6021 (pISSN: 0264-6021, eISSN: 1470-8728)
Title: The Biochemical journal
Title(ISO): Biochem J
Publisher: Portland Press, Ltd.
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 394 [継承]
(必須): Pt 2 [継承]
(必須): 501 509 [継承]
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年月日 (必須): 西暦 2006年 3月 1日 (平成 18年 3月 1日) [継承]
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DOI (任意): 10.1042/BJ20051197    (→Scopusで検索) [継承]
PMID (任意): 16302845    (→Scopusで検索) [継承]
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備考 (任意): 1.(英) PublicationType: Journal Article  (日)    [継承]
2.(英) PublicationType: Research Support, Non-U.S. Gov't  (日)    [継承]

標準的な表示

和文冊子 ● Julie Dunys, Toshitaka Kawarai, Sherwin Wilk, Peter George-Hyslop St, Cristine da Costa Alves and Frédéric Checler : Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins., The Biochemical Journal, Vol.394, No.Pt 2, 501-509, 2006.
欧文冊子 ● Julie Dunys, Toshitaka Kawarai, Sherwin Wilk, Peter George-Hyslop St, Cristine da Costa Alves and Frédéric Checler : Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins., The Biochemical Journal, Vol.394, No.Pt 2, 501-509, 2006.

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