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Molecular mechanism of transcriptional regulation forDNA repair genes: Identification of partner proteins for CXXC5, a novel MLH1 transcriptional factor

Research Project

Project/Area Number 22591495
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionToho University

Principal Investigator

ARITA Michitsune  東邦大学, 医学部, 助教 (80307719)

Co-Investigator(Renkei-kenkyūsha) KANNO Shin-ichiro  東北大学, 加齢医学研究所, 講師 (10400417)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords小腸大腸肛門外科学 / 低酸素 / 腫瘍微小環境 / 転写制御 / MLH1 / CXXC5 / DNAミスマッチ修復遺伝子 / 低酸素状態 / SYF2 / hnRPH1 / 転写制御因子
Research Abstract

In this study, CXXC5, DNA-binding protein recognizing the FP3CAT site of MLH1 promoter, was identified as an activator of MLH1 transcription. Co-immunoprecipitation and LC/MS/MS analysis revealed that CXXC5 and SYF2, previously screened as an FP3 site-binding protein, share common interacting protein HNRNPH1 and may co-operatively trans-activate MLH1. In hypoxia, all three protein levels were down-regulated and endogenous over-expression of them partially rescued MLH1 down-regulation. Hypoxic down-regulationof MLH1 may be mediated by CXXC5, SYF2, and HNRNPH1.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (22 results)

All 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (18 results)

  • [Journal Article] Down-regulation of MutS homolog 3 by hypoxia in human colorectal cancer2012

    • Author(s)
      Li J, Koike J, Kugoh H, Arita M, Ohhira T, Kikuchi Y, Funahashi K, Takamatsu K, Boland CR, Koi M, Hemmi H
    • Journal Title

      Biochim Biophys Acta -Molecular Cell Research

      Volume: 1823(4) Issue: 4 Pages: 889-899

    • DOI

      10.1016/j.bbamcr.2012.01.017

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients2011

    • Author(s)
      Mizuiri S, Hemmi H, et al
    • Journal Title

      Int J Nephrol

      Volume: 2011 Pages: 2610401-5

    • DOI

      10.4061/2011/261040

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Urinary angiotensin-converting enzyme 2 in patients with CKD2011

    • Author(s)
      Mizuiri S, Aoki T, Hemmi H, Arita M, Sakai K, and Aikawa A
    • Journal Title

      Nephrology(Carlton)

      Volume: 16(6) Issue: 6 Pages: 567-72

    • DOI

      10.1111/j.1440-1797.2011.01467.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy2011

    • Author(s)
      Mizuiri S, Hemmi H, Arita M, Aoki T, Ohashi Y, Miyagi M, Sakai K, Shibuya K, Hase H, and Aikawa A.
    • Journal Title

      Nephron Clin Prac

      Volume: 117(1) Issue: 1 Pages: c57-c66

    • DOI

      10.1159/000319648

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] DNA ミスマッチ修復遺伝子 MSH3による EMAST 腫瘍発生の分子機構2012

    • Author(s)
      有田通恒,児井稔,久郷裕之,近藤元就,逸見仁
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Hypoxic down-regulation of DNA mismatch repair gene hMSH3 and genetic instability of colorectal cancer2012

    • Author(s)
      Hemmi H, Arita M, Koike J, Kikuchi Y, Funahashi K, Ohira T, Kugoh H, Kondo M
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] 低酸素による hMLH1 発現抑制時の転写因子CXXC5, SYF2 およびhnRPH1 の関与2011

    • Author(s)
      有田通恒,李傑,菅野新一郎,菊池由宣,安井明,近藤元就,逸見仁道
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 低酸素によるhMLH1発現抑制時の転写因子CXXC5,SYF2およびhnRNPH1の関与2011

    • Author(s)
      有田通恒
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] N-myc非増幅神経芽腫細胞における N-myc の役割2011

    • Author(s)
      李傑,有田通恒,柴田祐充子,岩崎維和夫,黒岩実,近藤元就,逸見仁道
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋
    • Year and Date
      2011-11-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 低酸素による hMLH1 発現抑制における SYF2 おより hnRPH1 の役割2011

    • Author(s)
      有田通恒,李傑,安井明,近藤元就,逸見仁道
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2012 Final Research Report
  • [Presentation] 低酸素によるhMLH1発現抑制におけるSYF2およびhnRPH1の役割2011

    • Author(s)
      有田通恒
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 大腸がん由来細胞株におけるhMSH3 転写制御機構2010

    • Author(s)
      李傑,有田通恒,児井稔,逸見仁道
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2012 Final Research Report
  • [Presentation] CXXC5 と SYF2/p29 によるhMLH1 転写制御2010

    • Author(s)
      有田通恒,李傑,菅野新一郎,安井明,逸見仁道
    • Organizer
      第33回日本分子生物学会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] CXXC5とSYF2/p29によるhMLH1転写制御2010

    • Author(s)
      有田通恒
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Regulation of MMR genes and stem cell markers in hypoxia in colorectal cancer cells.2010

    • Author(s)
      Li J, Arita M, Koike J, Hemmi H
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH12010

    • Author(s)
      Arita M, Li J, Yasui A, Hemmi H
    • Organizer
      A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH1
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH12010

    • Author(s)
      有田通恒
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腎 ACE2 発現低下は糖尿病腎症に特異的か?2010

    • Author(s)
      水入苑生,逸見仁道,有田通恒,酒井謙,大橋靖,田中仁英,服部吉成,鈴木康紀,渋谷和俊,相川厚
    • Organizer
      第53回日本腎臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2010-06-17
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト尿細管上皮細胞におけるブドウ糖,ヒト血清アルブミンによる ACE2 発現の変化2010

    • Author(s)
      青木敏行,水入苑生,有田通恒,逸見仁道,大谷隆俊,鈴木康紀,服部吉成,田中仁英,大橋靖,酒井謙,相川厚
    • Organizer
      第53回日本腎臓学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2010-06-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Hypoxic down-regulation of DNA mismatch repair gene hMSH3 and genetic instability of colorectal cancer

    • Author(s)
      Hemmi Hiromichi
    • Organizer
      71st Annual Meeting of Japan Cancer Association
    • Place of Presentation
      ロイトン札幌,さっぽろ芸文館(札幌)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 神経芽腫における低酸素下でのMAPK経路によるN-mycの活性化

    • Author(s)
      逸見仁道
    • Organizer
      第54回日本小児血液・がん学会学術集会
    • Place of Presentation
      パシフィコ横浜会議センター(横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] DNAミスマッチ修復遺伝子MSH3によるEMAST腫瘍発生の分子機構

    • Author(s)
      有田通恒
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場,マリンメッセ福岡(福岡)
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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