• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Functional analysis of Th-POK in T cell development

Research Project

Project/Area Number 18590472
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionResearch Institute, International Medical Center of Japan

Principal Investigator

SUZUKI Harumi  Research Institute, International Medical Center of Japan, Department of Pathology, Director (70235985)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsT lymphocyte / ThPOK / transcription factor / signal transduction / CD4 / CD8
Research Abstract

Zinc finger transcription factor Th-POK has been identified as a master regulator of CD4/CD8 lineage commitment in the thymus. It is required for the differentiation of CD4 single positive T cells and its expression converts lineage fate from CD8-SP to CD4-SP. Despite the interesting phenotypes of Th-POK mutant mice, its function in thymocyte lineage commitment is completely unknown. In order to investigate the function of each domain of Th-POK, we introduced various mutant Th-POK cDNAs into Pax5 deficient proB cells and reconstituted the thymus with these cells. We found that the lineage converting activity of Th-POK requires its BTB domain and Zn finger domain. In order to identify downstream targets of Th-POK, we next performed chromatin immunoprecipitation experiments using anti-Th-POK antibody. By this method we found that Th-POK binds directly to the distal promoter region of the Runx3 gene. Therefore Th-POK could directly suppress expression of Runx3, which is required for CD4 repression in DP thymocyte. Furthermore, we found that calcium ionophore as well as some apoptosis inducing agents induced transcription of Th-POK in unsignaled DP thymocytes. Induction of apoptosis in DP thymocytes is induced by strong TCR-signals and differentiation to CD4-SP lineage requires a stronger (or longer) TCR-signal than the one required for the CD8-SP lineage. Therefore, it would be interesting if induction of Th-POK and induction of apoptosis share some part of the same signaling pathway in DP thymocytes.

Report

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

    (32 results)

All 2007 2006 Other

All Journal Article (20 results) (of which Peer Reviewed: 10 results) Presentation (9 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Melanocortin receptor 2 is required for adrenal gland development, steroidogenesis and neonatal gluconeogenesis2007

    • Author(s)
      Dai Chida, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 104

      Pages: 18205-18210

    • 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 p85a regulatory subunit of classIA phosphoinositide 3-kinase regulates b-selection in thymocyte developmentase2007

    • Author(s)
      Fumiko Shiroki, et al.
    • Journal Title

      J. Immunol. 178

      Pages: 1349-1356

    • 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] Racl mediated Bcl-2 induction is critical in antigen-induced CD4 single positive differentiation of a CD4+CD8+ immature thymocyte line2007

    • Author(s)
      Hiroyo Oda, et al.
    • Journal Title

      J. Leuko. Biol. 81

      Pages: 500-508

    • 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] Chlamydial SET domain protein functions as a histone methyltransferase2007

    • Author(s)
      Masayuki Murata, et al
    • Journal Title

      Microbiology 153

      Pages: 585-592

    • 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] Chlamydial SET domain protein functions as a histone methyltransferase2007

    • Author(s)
      Masayuki Murata, Yoshinao Azuma, Koshiro Miura, Mohd. Akhlakur Rahman, Minenosuke Matsutani, Masahiro Aoyama, Harumi Suzuki, Kazuro Sugi, Mutsunori Shirai
    • Journal Title

      Microbiology 153

      Pages: 585-592

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Rac1 mediated Bcl-2 induction is critical in antigen-induced CD4 single positive differentiation of a CD4+CD8+ immature thymocyte line2007

    • Author(s)
      Hiroyo Oda, Harumi Suzuki^*, Kouhei Sakai, Seiji Kitahara, Michael S. Patrick, Yoshinao Azuma, Kazuro Sugi, Toshio Kitamura, Jonathan Kaye, Mutsunori Shirai ^* [Corresponding auhtor]
    • Journal Title

      J. Leuko. Biol. 81

      Pages: 500-508

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The p85a regulatory subunit of classIA phosphoinositide 3-kinase regulates b-selection in thymocyte developmentase2007

    • Author(s)
      Fumiko Shiroki, Satoshi Matsuda, Tomomitsu Doi, Mari Fujiwara, Yoshito Mochizuki, Takashi Kadowaki, Harumi Suzuki, Shigeo Koyasu
    • Journal Title

      J. Immunol. 178

      Pages: 1349-1356

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Melanocortin receptor 2 is required for adrenal gland development, steroidogenesis and neonatal gluconeogenesis.2007

    • Author(s)
      Dai Chida, Shinichi Nakagawa, So Nagai, Hiroshi Sagara, Harumi Katsumata, Toshihiro Imaki, Harumi Suzuki, Fumiko Mitani, Tadashi Ogishima, Chikara Shimizu, Hayato Kotaki, Shigeru Kakuta, Katsuko Sudoa, Takao Koike, Mitsumasa Kubo, Yoichiro Iwakura
    • Journal Title

      Proc. Natl. Acad. Sci. USA 104

      Pages: 18205-18210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Melanocortin receptor 2 is required for adrenal gland development,steroi dogenesis and neonatal gluconeogenesis2007

    • Author(s)
      Dai Chida, et. al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 104

      Pages: 18205-18210

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The p85a regulatory subunit of classIA phosphoinositide 3-kinase regulates b-selection in thymocyte developmentase2007

    • Author(s)
      Fumiko Shiroki, et. al.
    • Journal Title

      J.Immunol. 178

      Pages: 1349-1356

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Racl mediated Bcl-2 induction is critical in antigen-induced CD4 single positive differentiation of a CD4+CD8+immature thymocyte line2007

    • Author(s)
      Hiroyo Oda, et. al.
    • Journal Title

      J.Leuko.Biol. 81

      Pages: 500-508

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The p85a regulatory subunit of classIA phosphoinositide 3-kinase regulates b-selection in thymocyte development2007

    • Author(s)
      Fumiko Shiroki, et al.
    • Journal Title

      J. Immunol. 178

      Pages: 1349-1356

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rac1 mediated Bc1-2 induction is critical in antigen-induced CD4 single positive differentiation of a CD4+CD8+ immature thymocyte line2007

    • Author(s)
      Hiroyo Oda, et al.
    • Journal Title

      J. Leuko. Biol. 81

      Pages: 500-508

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chlamydial SET domain protein functions as a histone methyltransferase2007

    • Author(s)
      Masayuki Murata, et al.
    • Journal Title

      Microbiology 153

      Pages: 585-592

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Phosphoinositide 3-Kinase in nitric oxides synthesis in macrophage : critical dimerization of inducible nitric oxide synthase2006

    • Author(s)
      Kouhei Sakai, et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 17736-17742

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cross-positive selection of thymocytes expressing a single T cell receptor by multiple major histocompatibility complex molecules of both classes : Implications for CD4+ vs. CD8+ lineage commitment2006

    • Author(s)
      Koji Eshima, et al.
    • Journal Title

      J. Immunol. 176

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome sequence of the cat pathogen, Chlamydophila felis2006

    • Author(s)
      Yoshinao Azuma, et al.
    • Journal Title

      DNA Research 13

      Pages: 15-23

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cross-positive selection of thymocytes expressing a single T cell receptor by multiple major histocompatibility complex molecules of both classes : Implications for CD4+ vs. CD8+ lineage commitment2006

    • Author(s)
      Koji Eshima, Harumi Suzuki, Nobukata Shinohara
    • Journal Title

      J. Immunol. 176

      Pages: 1628-1636

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Genome sequence of the cat pathogen, Chlamydophila felis2006

    • Author(s)
      Yoshinao Azuma, Hideki Hirakawa, Atsushi Yamashita, Yan Cai, Mohd Akhlakur Rahman, Harumi Suzuki, Shigeki Mitaku, Hidehiro Toh, Susumu Goto, Tomoyuki Murakami, Kazuro Sugi, Hideo Hayashi, Hideto Fukushi, Masahira Hattori, Satoru Kuhara, Mutsunori Shirai
    • Journal Title

      DNA Research 13

      Pages: 15-23

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phosphoinositide 3-Kinase in nitric oxides synthesis in macrophage : critical dimerization of inducible nitric oxide synthase2006

    • Author(s)
      Kouhei Sakai, Harumi Suzuki^*. Hiroyo Oda, Takaaki Akaike, Yoshinao Azuma, Tomoyuki Murakami, Kazuro Sugi, Takehito Ito, Hiroshi Ichinose, Shigeo Koyasu, Mutsunori Shirai ^* [Corresponding auhtor]
    • Journal Title

      J. Biol. Chem. 281

      Pages: 17736-17742

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FUNCTION OF RHOH IN T CELL DEVELOPMENT2007

    • Author(s)
      Hiroyo Oda, et al.
    • Organizer
      Rolduc Workshop on T cell Biology
    • Place of Presentation
      Kerkrade, Netherland
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Function of RhoH in T cell development and activation2007

    • Author(s)
      Hiroyo Oda, Michael Patrick, Yoshinori Sato, Dai Chida, Takehiko Sasazuki, Mutsunori Shirai, Harumi Suzuki
    • Organizer
      37th Annual meeting of Japanese Societ of Immunology
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of RhoH in T cell develoopment2007

    • Author(s)
      Hiroyo Oda, Michael Patrick, Yoshinori Sato, Kohei Sakai, Seiji Kitahara, Shinichi Aizawa, Mutsunori Shirai, Harumi Suzuki
    • Organizer
      17th Anual meeting of KTCC
    • Place of Presentation
      Kyoto
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FUNCTION OF RHOH IN T CELL DEVELOPMENT2007

    • Author(s)
      Hiroyo Oda, Michael S. Patrick, Yoshinori Sato, Kohei Sakai, Takehiko Sasazuki, Sinichi Aizawa, Mutsunori Shirai, Harumi Suzuki
    • Organizer
      Rolduc Workshop on T cell Bilogy
    • Place of Presentation
      Kerkrade, Netherland
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FUNCTION OF RHOH IN T CELL DEVELOPMENT2007

    • Author(s)
      Hiroyo Oda, et. al.
    • Organizer
      Rolduc Workshop on T cell Biology
    • Place of Presentation
      Kerkrade,Netherland
    • Related Report
      2007 Annual Research Report
  • [Presentation] Role of Rac1 in survival of peripheral T cells2006

    • Author(s)
      ODA Hiroyo, SUZUKI Harumi, BABA Yukari, SAKAI Kouhei, PATRICK Michael, KITAHARA Seiji, AIZAWA Shin-ichi, SHIRAI Mutsunori
    • Organizer
      36th Annual meeting of Japanese Societ of Immunology
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of Th-POK in T cell development2006

    • Author(s)
      SUZUKI Harumi, SAKAI Kouhei, SHIRASAKI Tomoaki, ODA Hiroyo, KITAHARA Seiji, PATRICK S. Michael, GALERA Philippe, SHIRAI Mutsunori
    • Organizer
      36th Annual meeting of Japanese Societ of Immunology
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Phosphoinositide 3-kinase in nitric oxides synthesis in macrophage : critical dimerization of inducible nitric oxide synthase2006

    • Author(s)
      Harumi Suzuki, Kouhei Sakai, Takaaki Akaike, Shigeo Koyasu, Mutsunori Shirai
    • Organizer
      6th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Anlaysis of expression and function of Th-POK in DP thymocytes2006

    • Author(s)
      Harumi Suzuki, Kouhei Sakai, Tomoaki Shirasaki, Hiroyo Oda, Seiji Kitahara, Michael S. Patrick, Mutsunori Shirai
    • Organizer
      16th Anual meeting of KTCC
    • Place of Presentation
      Kyoto
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 「Annual Review 免疫2006」奥村康、平野俊夫編2006

    • Author(s)
      鈴木春巳
    • Total Pages
      11
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.imcj.go.jp/rese/top/j/rese_path.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.imcj.go.jp/rese/top/j/rese_path.html

    • Related Report
      2007 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi