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

• Project/Area Number: 22591495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Toho 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: ¥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.

Research Products

• [Journal Article] Down-regulation of MutS homolog 3 by hypoxia in human colorectal cancer (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Effluent markers related to epithelial mesenchymal transition with adjusted values for effluent cancer antigen 125 in peritoneal dialysis patients (2011)
  • Author(s): Mizuiri S, Hemmi H, et al
  • Journal Title: Int J Nephrol Volume: 2011 Pages: 2610401-5
  • DOI: 10.4061/2011/261040
  • Peer Reviewed
• [Journal Article] Urinary angiotensin-converting enzyme 2 in patients with CKD (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy (2011)
  • 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
  • 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
• [Presentation] Hypoxic down-regulation of DNA mismatch repair gene hMSH3 and genetic instability of colorectal cancer (2012)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH1 (2010)
  • 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
• [Presentation] A novel transcriptional regulator, CXXC5 zinc finger protein, for a DNA mismatch repair gene, hMLH1 (2010)
  • 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
• [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
• [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
• [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）
• [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）
• [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）