Study on functional significance of transcription factor GATA-6during oncogenic signal transduction

• Project/Area Number: 22501007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Shinshu University
• Principal Investigator: ADACHI Yoshifumi 信州大学, 医学部, 准教授 (50201893)
• Co-Investigator(Kenkyū-buntansha): KAMATA Tohru 信州大学, 医学部, 教授 (40056304)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 転写因子 / GATA-6 / シグナル伝達 / ＧＡＴＡ-6 / ＴＯＰＯＲＳ / TOPORS / Nox1

Research Abstract

We clarified that phosphorylation of GATA-6 and GATA-6-associated cofactor HMGB1 positively regulate the transcriptional machinery for Nox1 gene in oncogenic Ras signaling. We identified 719 genes upregulated byGATA-6 and 1161 genes downregulated by GATA-6 in colon cancer cell-line CaCo-2. We also clarified the molecular mechanism for transcriptional repression of TOPORS gene by GATA-6.

Research Products

• [Journal Article] TA strategy for site-directed mutagenesis (2012)
  • Author(s): Adachi Y., Fukuhara C.
  • Journal Title: Anal. Biochem Volume: Vol.431 Pages: 66-68
  • URL: http://dx.DOI:.org/10.1016/j.ab.2012.08.030
  • Peer Reviewed
• [Journal Article] Acrucial role for Nox 1 in redox-dependent regulation of Wnt-b-catenin signaling. (2012)
  • Author(s): Kajla S., Mondol AS., Nagasawa A., Zhang Y., Kato M., Matsuno K., Yabe-Nishimura C., Kamata T.
  • Volume: Vol .26、No.5
  • Pages: 2049-2059
  • URL: http://www.fasebj.org/content/26/5/2049.long
  • Peer Reviewed
• [Journal Article] TA strategy for rapid and efficient site-directed mutagenesis (2012)
  • Author(s): Yoshifumi Adachi
  • Journal Title: Analytical Biochemistry Volume: ４３１ Pages: 66-68
  • Peer Reviewed
• [Journal Article] Reactive oxygen generated by NADPH oxidase 1 (Nox1) contributes to cell invasion by regulating matrix metalloprotease-9 production and cell migration. (2010)
  • Author(s): Shinohara M., Adachi Y., Mitsushita J., Kuwabara M., Nagasawa A., Harada S., Furuta S., Zhang Y., Seheli K., Miyazaki H., Kamata T
  • Volume: Vol .285、No.7
  • Pages: 4481-4488
  • NAID: 120002696305
  • URL: http://www.jbc.org/content/285/7/4481
  • Peer Reviewed
• [Journal Article] Reactive Oxygen Generated by NADPH Oxidase 1(Nox1)Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration. (2010)
  • Author(s): Shinohara Masahiro
  • Journal Title: J.Biol. Chem. Volume: 285 Pages: 4481-4488
  • Peer Reviewed
• [Presentation] High mobility group protein- B1 (HMGB1) is a novel activator of GATA-6 in the transcriptional machinery for NADPH oxidase1. (2012)
  • Author(s): 安達喜文
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2012-12-16
• [Presentation] Transcriptional repression of TOPORS gene expression by GATA-6. (2012)
  • Author(s): 安達喜文
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(札幌市)
  • Year and Date: 2012-09-20
• [Presentation] 発癌のシグナル伝達におけるTOPORS の機能的役割:Functional characterization of GATA-6-regulated TOPORS in oncogenic signal transduction (2011)
  • Author(s): 安達喜文
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2011-09-23
• [Presentation] 発癌のシグナル伝達におけるTOPOSの機能的役割 : Functional characterization of GATA-6-regulated TOPORS in oncogenic signal transduction (2011)
  • Author(s): 安達喜文
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2011-09-23
• [Presentation] Regulatory mechanism of Ras-ERK signaling-responsive transcript- tion factor GATA-6 that mediates the expression of NADPH oxidase (Nox) 1 (2010)
  • Author(s): 安達喜文
  • Organizer: 第83回日本生化学会・第33回に本分子生物学会年会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-08
• [Presentation] Regulatory mechanism of Ras-ERK signaling-responsive transcription factor GATA-6 that mediates the expression of NADPH oxidase(Nox)1. (2010)
  • Author(s): 安達喜文
  • Organizer: 第83回日本生化学会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-08
• [Presentation] Regulation of the NADPH oxidase 1 gene expression by the GATA-6 (2010)
  • Author(s): 安達喜文
  • Organizer: 第60回藤原セミナー国際シンポジウ「Zinc signaling and cellular functions」
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-10-29
• [Presentation] Regulation of the NADPH oxidase 1 gene expression by the GATA-6. (2010)
  • Author(s): 安達喜文
  • Organizer: 第60回藤原セミナー国際シンポジウム「Zinc signaling and cellular functions」
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-10-29
• [Presentation] Ras/ERKシグナルによるGATA-6のリン酸化とNADPHオキシダーゼ1(Nox1)遺伝子発現の制御機構 (2010)
  • Author(s): 安達喜文
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-09-22
• [Presentation] Transcriptional repression of TOPORS gene expression by GATA-6.
  • Author(s): 安達喜文
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（札幌市）
• [Presentation] High mobility group protein-B1 (HMGB1) is a novel activator of GATA-6 in the transcriptional machinery for NADPH oxidase 1.
  • Author(s): 安達喜文
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡市）