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The Role in APC stability control mechanism by EDD

Research Project

Project/Area Number 18591486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionSt.Marianna University School of Medicine

Principal Investigator

OTSUBO Takehito  St.Marianna University School of Medicine, Department of Surgery, Professor (50398971)

Co-Investigator(Kenkyū-buntansha) OHTA Tomohiko  St. Marianna University School of Medicine, Department of Surgery, Associate Professor (60233136)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordstumor suppressor / hyd / EDD / 家族性大腸ポリポーシス / colon cancer / APC
Research Abstract

Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a key player in the Wnt signaling pathway. While the role of APC in inhibition of β-catenin/LEF1-dependent activation of transformation-inducing genes has been intensively studied and well established, regulation of APC expression at the protein level is only partially understood. Here we report that APC is up-regulated by EDD, the mammalian orthologue of Drosophila melanogaster hyperplastic discs gene (hyd) that is considered to be a putative tumor suppressor. Screening of APC immunocomplexes by mass spectrometry identified EDD as a putative APC-interacting protein. Exogenously expressed and endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Overexpression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of □-catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein level without altering its mRNA level, causing enhanced protein expression of □-catenin. Thus through protein-protein interaction, EDD stabilizes APC and up-regulates APC's function to inhibit □-catenin, suggesting that EDD could act as a colorectal tumor suppressor.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (40 results)

All 2008 2007 2006

All Journal Article (30 results) (of which Peer Reviewed: 12 results) Presentation (10 results)

  • [Journal Article] The Role of the New Ca2+ Antagonist,CV159,in Hepatic I/R Injury-The Evaluation of Hepatic Organ Reducing Activity Using In Vivo and Ex Vivo EPR2008

    • Author(s)
      Taiji Watanabe, et. al.
    • Journal Title

      Journal of Surgical Research. 145

      Pages: 49-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The ubiquitin E3 ligase activity of BRCA1 and its biological functions2008

    • Author(s)
      Wu W, et. al.
    • Journal Title

      Cell Div. 7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis2008

    • Author(s)
      Shimo A, et. al.
    • Journal Title

      Cancer Sci. 99(1)

      Pages: 62-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis.2008

    • Author(s)
      Shimo A, Tanikawa C, Nishidate T, Lin ML, Matsuda K, Park JH, Ueki T, Ohta T, Hirata K, Fukuda M, Nakamura Y, Katagiri T.
    • Journal Title

      Cancer Sci. 99(1)

      Pages: 62-70

    • NAID

      10024000927

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The ubiquitin E3 ligase activity of BRCA1 and its biological functions.2008

    • Author(s)
      Wu W, Koike A, Takeshita T, Ohta T.
    • Journal Title

      Cell Div. Jan 7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Role of the New Ca2+ Antagonist, CV159, in Hepatic I/R Injury-The Evaluation of Hepatic Organ Reducing Activity Using In Vivo and Ex Vivo EPR.2008

    • Author(s)
      Taiji Watanabe, Shigeru Oowada, Hiromichi P. Kobayashi, Masato Kamibayashi, Atsuko Ishiuchi, Yuji Jinnouchi, Satoshi Koizumi, Takayuki Asano, Tsukasa Shimamura, Takeshi Asakura, Hiroshi Nakano, Sunao Kubota, Takehito Otsubo.
    • Journal Title

      Journal of Surgical Research 145

      Pages: 49-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Role of the New Ca2+ Antagonist, CV159, in Hepatic I/R Injury-The Evaluation of Hepatic Organ Reducing Activity Using In Vivo and Ex Vivo EPR2008

    • Author(s)
      Taiji Watanabe, et. al.
    • Journal Title

      Journal of Surgical Research 145

      Pages: 49-56

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Putative tumor suppressor EDD interacts with and up-regulates APC2007

    • Author(s)
      Ohshima R, et. al.
    • Journal Title

      Genes Cells. 12(12)

      Pages: 1339-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver2007

    • Author(s)
      Oshima R, et. al.
    • Journal Title

      Eur Surg Res. 40(3)

      Pages: 247-255

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Predictive markers in breast cancer treatment-focusing on a recent topic "basal-like breast cancer"2007

    • Author(s)
      Koike A, et. al.
    • Journal Title

      Nippon Rinsho. 65 Suppl 6

      Pages: 285-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Breast and ovarian cancer susceptibility product BRCA12007

    • Author(s)
      Ohta T.
    • Journal Title

      Protein Nucleic Acid and Enzyme (PNE) 51

      Pages: 1395-1400

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'.2007

    • Author(s)
      Yamasaki S, et. al.
    • Journal Title

      EMBO J. 26

      Pages: 113-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Elevated expression of PRC1,involved in the growth of breast cancer cells.2007

    • Author(s)
      Shimo A, et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 174-81

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] BRCA1 ubiquitinates RPB8 in response to DNA damage2007

    • Author(s)
      Wu W, et. al.
    • Journal Title

      Cancer Res. 67(3)

      Pages: 951-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] BRCA1 ubiquitinates RPB8 in response to DNA damage.2007

    • Author(s)
      Wu W, Nishikawa H, Hayami R, Sato K, Honda A, Aratani S, Nakajima T, Fukuda M, Ohta T.
    • Journal Title

      Cancer Res. 67(3)

      Pages: 951-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Elevated expression of PRC1, involved in the growth of breast cancer ells.2007

    • Author(s)
      Shimo A, Nishidate T, Ohta T, Fukuda M, Nakamura Y, Katagiri T.
    • Journal Title

      Cancer Sci. 98

      Pages: 174-81

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase'Synoviolin'.2007

    • Author(s)
      Yamasaki S, Yagishita N, Sasaki T, Nakazawa M, Kato Y, Yamadera T, Bae E, Toriyama S, Ikeda R, Zhang L, Fujitani K, Yoo E, Tsuchimochi K, Ohta T, Araya N, Fujita H, Aratani S, Eguchi K, Komiya S, Maruyama I, Higashi N, Sato M, Senoo H, Ochi T, Yokoyama S, Amano T, Kim J, Gay S, Fukamizu A, Nishioka K, Tanaka K, Nakajima T.
    • Journal Title

      EMBO J. 26

      Pages: 113-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Predictive markers in breast cancer treatment-focusing on a recent topicbasal-like breast cancer2007

    • Author(s)
      Koike A, Ohta T.
    • Journal Title

      Nippon Rinsho.(Suppl 6) 65

      Pages: 285-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver.2007

    • Author(s)
      Oshima R, Nakano H, Katayama M, Sakurai J, Wu W, Koizumi S, Asano T, Watanabe T, Asakura T, Ohta T, Otsubo T.
    • Journal Title

      Eur Surg Res. 40(3)

      Pages: 247-255

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Putative tumor suppressor EDD interacts with and up-regulates APC.2007

    • Author(s)
      Ohshima R, Ohta T, Wu W, Koike A, Iwatani T, Henderson M, Watts CK, Otsubo T.
    • Journal Title

      Genes Cells. 12(12)

      Pages: 1339-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Putative tumor suppressor EDD interacts with and up-regulates APC.2007

    • Author(s)
      Ohta, T, et. al.
    • Journal Title

      Genes Cells 12

      Pages: 1339-45

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver.2007

    • Author(s)
      Ohta T, et. al.
    • Journal Title

      Eur Surg Res 40(3)

      Pages: 247-255

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive markers in breast cancer treatment-focusing on a recent topic "basal-like breast cancer"2007

    • Author(s)
      Ohta T, et. al.
    • Journal Title

      Nippon Rinsho 65Suppl6

      Pages: 285-90

    • NAID

      40015531685

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BECA1 ubiquitinates RPB8 in response to DNA damage.2007

    • Author(s)
      Ohta T, et al.
    • Journal Title

      Cancer Res. 67(3)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elevated expression of PRC1,involved in the growth of breast cancer cells.2007

    • Author(s)
      Ohta T, er al
    • Journal Title

      Cancer Sci. 98

      Pages: 174-81

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'.2007

    • Author(s)
      Ohta T, er al
    • Journal Title

      EMBO J. 26

      Pages: 113-22

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Breast and ovarian cancer susceptibility product BRCA1.2006

    • Author(s)
      Ohta T.
    • Journal Title

      Protein Nucleic Acid and Enzyme(PNE) 51

      Pages: 1395-1400

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 乳癌および卵巣癌抑制遺伝子BRCA12006

    • Author(s)
      太田智彦, ほか
    • Journal Title

      PNE : 蛋白核酸酵素 51

      Pages: 1395-1400

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肝門部胆管癌に対する左葉尾状葉切除2006

    • Author(s)
      大坪毅人
    • Journal Title

      消化器外科 第29巻第12号

      Pages: 1645-1654

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protein pattern difference in the colon cancer cell lines examined b two-dimensional differential in-gelexectrophiresis and mass spectrometry2006

    • Author(s)
      大坪毅人, ほか
    • Journal Title

      Surg Today 36

      Pages: 1085-1093

    • Related Report
      2006 Annual Research Report
  • [Presentation] Cooperation of BRCA1 and ubiquitin in the DNA damage response2008

    • Author(s)
      Ohta T.
    • Organizer
      The 23rd Nagoya international cancer treatment symposium
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-01-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular functions of BRCA1 E3 ubiquitin ligase in cell cycle and DNA damage response2007

    • Author(s)
      Ohta T.
    • Organizer
      The 66th annual meeting of the Japanese cancer association
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular functions of BRCA1E3 ubiquitin ligase in cell cycle and DNA damage response2007

    • Author(s)
      Ohta T., Wu W, Fukuda M.
    • Organizer
      The 66th annual meeting of the Japanese cancer association
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ubiquitin ligase activity of BRCA1,a hub protein that regulates multiple cellular pathways2006

    • Author(s)
      Ohta T.
    • Organizer
      MBSJ forum 2006 of the molecular biology society of Japan
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-12-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ubiquitin ligase activity of BRCA1, a hub protein that regulates multiple cellular pathways2006

    • Author(s)
      Ohta T., Wu W, Fukuda M.
    • Organizer
      MBSJ forum 2006 of the molecular biology society of Japan
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-12-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of BRCA1's Enzyme Activity in the Maintenance of Genomic Stability2006

    • Author(s)
      Ohta T.
    • Organizer
      The 49th annual meeting of the Japan radiation research society
    • Place of Presentation
      Sapporo
    • Year and Date
      2006-09-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Breast and ovarian tumor suppression by BRCA1's enzyme activity2006

    • Author(s)
      Ohta T.
    • Organizer
      The 43th congress of the Japanese society of molecular medicine
    • Place of Presentation
      Sapporo
    • Year and Date
      2006-07-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The enzyme activity of breast and ovarian tumor suppresser BRCA12006

    • Author(s)
      Ohta T.
    • Organizer
      The 12th annual congress of the Japanese society for familial tumors
    • Place of Presentation
      Suita
    • Year and Date
      2006-06-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The enzyme activity of breast and ovarian tumor suppresser BRCA12006

    • Author(s)
      Ohta T.
    • Organizer
      The 95th annual congress of the Japanese society of pathology
    • Place of Presentation
      Sinjuku
    • Year and Date
      2006-04-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of BRCA1's enzyme activity in breast and ovarian tumor Suppression2006

    • Author(s)
      Ohta T.
    • Organizer
      The 95th annual congress of the Japanese society of pathology
    • Place of Presentation
      Siniuku
    • Year and Date
      2006-04-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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