| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○著者 (必須): | 1. | (英) Hirano Takahiro (日) (読)
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| 2. | 村上 太一
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| 3. | (英) Ono Hiroyuki (日) (読)
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| 4. | 櫻井 明子 ([徳島大学.大学院医歯薬学研究部.保健学域.保健科学部門.医用検査学系.微生物・遺伝子解析学])
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| 5. | 冨永 辰也 ([徳島大学.大学院医歯薬学研究部.保健学域.保健科学部門.医用検査学系.細胞・免疫解析学])
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| 6. | 髙橋 利和
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| 7. | 長井 幸二郎
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| 8. | 土井 俊夫
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| 9. | 安部 秀斉
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| ○題名 (必須): | □ | (英) A Novel Interaction between FLICE-Associated Huge Protein (FLASH) and E2A Regulates Cell Proliferation and Cellular Senescence via Tumor Necrosis Factor (TNF)-Alpha-p21WAF1/CIP1 Axis. (日)
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| ○要約 (任意): | □ | (英) Dysregulation of the cell proliferation has been implicated in the pathophysiology of a number of diseases. Cellular senescence limits proliferation of cancer cells, preventing tumorigenesis and restricting tissue damage. However, the role of cellular senescence in proliferative nephritis has not been determined. The proliferative peak in experimental rat nephritis coincided with a peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded transcription factor) did not promote proliferation of Mesangial cells (MCs) by itself. We identified caspase-8-binding protein FLICE-associated huge protein (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening. Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did not affect p53 expression. Furthermore, overexpression of E12 and E47 induced p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A and p21 expression at the peak of proliferation was followed by significant induction of FLASH in mesangial areas in rat proliferative glomerulonephritis. Moreover, we revealed that FLASH negatively regulates cellular senescence via the interaction with E12. We also demonstrated that FLASH is involved in the TNF--induced p21 expressions. These results suggest that the functional interaction of E2A and FLASH play an important role in cell proliferation and cellular senescence via regulation of p21 expression in experimental glomerulonephritis. (日)
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| ○キーワード (推奨): |
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| ○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 oneTitle(ISO): PLoS OnePublisher: PLOS (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 10
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| ○号 (必須): | □ | 7
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| ○頁 (必須): | □ | e0133205 e0133205
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| ○年月日 (必須): | □ | 西暦 2015年 7月 24日 (平成 27年 7月 24日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1371/journal.pone.0133205 (→Scopusで検索)
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| ○PMID (任意): | □ | 26208142 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): | □ | 000358622000065
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| ○Scopus (任意): | □ | 2-s2.0-84941908247
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| ○備考 (任意): | 1. | (英) PublicationType: Journal Article (日)
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