『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]
招待 (推奨):
審査 (推奨): Peer Review [継承]
カテゴリ (推奨): 研究 [継承]
共著種別 (推奨): 国際共著 (徳島大学内研究者と国外研究機関所属研究者との共同研究) [継承]
学究種別 (推奨):
組織 (推奨): 1.徳島大学.先端酵素学研究所 (2016年4月1日〜) [継承]
著者 (必須): 1. (英) Jun Youn Do (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
2. (英) Kim Hyejin (日) (読)
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貢献度 (任意):
学籍番号 (推奨):
[継承]
3. (英) Jang Young Won (日) (読)
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貢献度 (任意):
学籍番号 (推奨):
[継承]
4. (英) Lee Young Ji (日) (読)
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学籍番号 (推奨):
[継承]
5.福井 清 ([徳島大学])
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貢献度 (任意):
学籍番号 (推奨):
[継承]
6. (英) Kim Ho Young (日) 金 英浩 (読) キム ヨンホ
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
題名 (必須): (英) Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells  (日)    [継承]
副題 (任意):
要約 (任意): (英) Human lysosomal-associated protein multispanning membrane 5 (LAPTM5) was identified by an ordered differential display-polymerase chain reaction (ODD-PCR) as an up-regulated cDNA fragment during 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of U937 cells into monocytes/macrophages. After TPA-treatment, the levels of LAPTM5 mRNA and protein increased and reached a maximum at 18-36 h. In healthy human tissues, LAPTM5 mRNA was expressed at high levels in hematopoietic cells and tissues, at low levels in the lung and fetal liver, and was not detected in other non-hematopoietic tissues. LAPTM5 mRNA was detected in immature malignant cells of myeloid lineage, such as K562, HL-60, U937, and THP-1 cells, and in unstimulated peripheral T cells, but was absent or barely detectable in lymphoid malignant or non-hematopoietic malignant cells. The LAPTM5 level in HL-60 cells increased more significantly during TPA-induced monocyte/macrophage differentiation than during DMSO-induced granulocyte differentiation. Ectopic expression of GFP-LAPTM5 or LAPTM5 in HeLa cells exhibited the localization of LAPTM5 to the lysosome. In HeLa cells overexpressing LAPTM5, the Mcl-1 and Bid levels declined markedly and apoptosis was induced via Bak activation, Δψm loss, activation of caspase-9, -8 and -3, and PARP degradation without accompanying necrosis. However, these LAPTM5-induced apoptotic events except for the decline of Bid level were completely abrogated by concomitant overexpression of Mcl-1. The pan-caspase inhibitor (z-VAD-fmk) could suppress the LAPTM5-induced apoptotic sub-G1 peak by ~40% but failed to block the induced Δψm loss, whereas the broad-range inhibitor of cathepsins (Cathepsin Inhibitor I) could suppress the LAPTM5-induced apoptotic sub-G1 peak and Δψm loss, by ~22% and ~23%, respectively, suggesting that the LAPTM5-mediated Δψm loss was exerted at least in part in a cathepsin-dependent manner. Together, these results demonstrate that ectopic overexpression of LAPTM5 in HeLa cells induced apoptosis via cleavage of Mcl-1 and Bid by a LAPTM5-associated lysosomal pathway, and subsequent activation of the mitochondria-dependent caspase cascade.  (日)    [継承]
キーワード (推奨): 1. (英) Apoptosis (日) (読) [継承]
2. (英) Down-Regulation (日) (読) [継承]
3. (英) Ectopic Gene Expression (日) (読) [継承]
4. (英) HeLa Cells (日) (読) [継承]
5. (英) Humans (日) (読) [継承]
6. (英) Lysosomes (日) (読) [継承]
7. (英) Membrane Proteins (日) (読) [継承]
8. (英) Mitochondria (日) (読) [継承]
9. (英) Myeloid Cell Leukemia Sequence 1 Protein (日) (読) [継承]
10. (英) bcl-2 Homologous Antagonist-Killer Protein (日) (読) [継承]
発行所 (推奨): (英) Public Library of Science (日) (読) [継承]
誌名 (必須): PLoS ONE (Public Library of Science)
(eISSN: 1932-6203)

ISSN (任意): 1932-6203
ISSN: 1932-6203 (eISSN: 1932-6203)
Title: PloS one
Title(ISO): PLoS ONE
Publisher: Public Library of Science
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 12 [継承]
(必須): 5 [継承]
(必須): e0176544 e0176544 [継承]
都市 (任意):
年月日 (必須): 西暦 2017年 5月 2日 (平成 29年 5月 2日) [継承]
URL (任意):
DOI (任意): 10.1371/journal.pone.0176544    (→Scopusで検索) [継承]
PMID (任意): 28464033    (→Scopusで検索) [継承]
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機関リポジトリ : 112313 [継承]
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備考 (任意): 1.(英) Article.ELocationID: 10.1371/journal.pone.0176544  (日)    [継承]
2.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]

標準的な表示

和文冊子 ● Do Youn Jun, Hyejin Kim, Won Young Jang, Ji Young Lee, Kiyoshi Fukui and Young Ho Kim : Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells, PLoS ONE, Vol.12, No.5, e0176544, 2017.
欧文冊子 ● Do Youn Jun, Hyejin Kim, Won Young Jang, Ji Young Lee, Kiyoshi Fukui and Young Ho Kim : Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells, PLoS ONE, Vol.12, No.5, e0176544, 2017.

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