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著作: Hasegawa, M/Imamura, R/[茂谷 康]/Nishiuchi, T/Matsumoto, N/Kinoshita, T/Suda, T/Mechanism and repertoire of ASC-mediated gene expression/[The Journal of Immunology]

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EID
287580
EOID
797893
Map
0
LastModified
2015年9月12日(土) 20:07:29
Operator
大家 隆弘
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TRUE
Censor
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Owner
茂谷 康
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
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) Hasegawa, M
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Imamura, R
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. 茂谷 康([徳島大学.先端酵素学研究所.基幹研究部門])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Nishiuchi, T
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Matsumoto, N
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Kinoshita, T
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Suda, T
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Mechanism and repertoire of ASC-mediated gene expression

副題 任意
要約 任意

(英) Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an adaptor molecule that mediates inflammatory and apoptotic signals. Although the role of ASC in caspase-1-mediated IL-1beta and IL-18 maturation is well known, ASC also induces NF-kappaB activation and cytokine gene expression in human cells. In this study, we investigated the molecular mechanism and repertoire of ASC-induced gene expression in human cells. We found that the specific activation of ASC induced AP-1 activity, which was required for optimal IL8 promoter activity. ASC activation also induced STAT3-, but not STAT1-, IFN-stimulated gene factor 3- or NF-AT-dependent reporter gene expression. The ASC-mediated AP-1 activation was NF-kappaB-independent and primarily cell-autonomous response, whereas the STAT3 activation required NF-kappaB activation and was mediated by a factor that can act in a paracrine manner. ASC-mediated AP-1 activation was inhibited by chemical or protein inhibitors for caspase-8, caspase-8-targeting small-interfering RNA, and p38 and JNK inhibitors, but not by a caspase-1 inhibitor, caspase-9 or Fas-associated death domain protein (FADD) dominant-negative mutants, FADD- or RICK-targeting small-interfering RNAs, or a MEK inhibitor, indicating that the ASC-induced AP-1 activation is mediated by caspase-8, p38, and JNK, but does not require caspase-1, caspase-9, FADD, RICK, or ERK. DNA microarray analyses identified 75 genes that were induced by ASC activation. A large proportion of them was related to transcription (23%), inflammation (21%), or cell death (16%), indicating that ASC is a potent inducer of inflammatory and cell death-related genes. This is the first report of ASC-mediated AP-1 activation and the repertoire of genes induced downstream of ASC activation.

キーワード 推奨
  1. (英) Caspase 8
  2. (英) Cell Line
  3. (英) Cytoskeletal Proteins
  4. (英) Gene Expression Profiling
  5. (英) Gene Expression Regulation
  6. (英) Humans
  7. (英) Interleukin-8
  8. (英) Mitogen-Activated Protein Kinases
  9. (英) Promoter Regions, Genetic
  10. (英) STAT3 Transcription Factor
  11. (英) Transcription Factor AP-1
発行所 推奨
誌名 必須 The Journal of Immunology([The American Association of Immunologists])
(pISSN: 0022-1767, eISSN: 1550-6606)
ISSN 任意 1550-6606
ISSN: 0022-1767 (pISSN: 0022-1767, eISSN: 1550-6606)
Title: Journal of immunology (Baltimore, Md. : 1950)
Title(ISO): J Immunol
Publisher: American Association of Immunologists
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 182
必須 12
必須 7655 7662
都市 任意
年月日 必須 2009年 6月 15日
URL 任意
DOI 任意 10.4049/jimmunol.0800448    (→Scopusで検索)
PMID 任意 19494289    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.4049/jimmunol.0800448

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't