Functional analysis of Th-POK in T cell development
| Project/Area Number |
18590472
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
SUZUKI Harumi Research Institute, International Medical Center of Japan, Department of Pathology, Director (70235985)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | T lymphocyte / ThPOK / transcription factor / signal transduction / CD4 / CD8 |
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| 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.
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Report
(3 results)
Research Products
(32 results)
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[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
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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
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[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
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Journal Title
DNA Research 13
Pages: 15-23
Description
「研究成果報告書概要(欧文)」より
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[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
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[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
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