Homepage of This Laboratory

Professor

Masanobu SATAKE

Associate Professor

Natsuko CHIBA

Assistant Professor

Syunsuke KON

One of the major principles in immunology is the specificity of antigen recognition by immunoglobulin or T cell receptor molecules on the cell surface. The expression of the genes encoding these molecules is regulated by transcription factors interacting with the enhancer/promoter regions of the genes. Research of our laboratory is focused on the function and role of transcription factors in the differentiation and tumorigenicity of immunocompetent cells.

The projects we are engaged in are as follows :

1. Functions of transcription factors in the development of hematopoietic stem cells and T lymphocytes.
2. Molecular mechanisms involved in the occurence of human acute myeloid leukemia.

The analytical tools we employ include not only conventional recombinant DNA technology and protein chemistry but also gene engineering of cells and embryos.

Publication list

1. Sato, T., Ito, R., Nunomura, S., Ono, S., Hayashi, K.,Satake, M. and Habu, S. Requirement of transcription factor AML1 in proliferation of developing thymocytes. Immunol. Letters. (in press)
2. Komine, O., Hayashi, K., Natsume, W., Watanabe, T., Seki, Y., Seki, N, Yagi, R., Sukzuki, W., Tamauchi, H., Hozumi, K., Habu, S., Kubo, M. and Satake, M. The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression. J. Exp. Med. (in press)
3. Shida, K., Terajima, D., Uchino, R., Ikawa, S., Ikeda, M., Asano, K., Watanabe, T., Azumi, K., Nonaka, M., Satou, Y., Satoh, N., Satake, M., Kawazoe, Y., .and Kasuya, A. Hemocytes of Ciona intestinalis express multiple genes involved in innate immune host defense. Biochem. Biophys. Res. Com. 302:207-218, 2003.
4. Terajima, D., Shida, K., Takada, N., Kasuya, A., Rokhsar, D., Satoh, N., Satake, M. and Wang, H-G. Idenification of candidate genes encoding the core components of the cell death machinery in the Ciona intestinalis genome. Cell Death Different. 10:749-753, 2003.
5. Dehal, P., Satou, Y., Campbell, R.K., -- Satake, M.(the 25th among the 87 authors) --- Levine, M., Satoh, N. and Rokhsar, D. The draft genome of Ciona intestinalis:Insights into chordate and vertebrate origins. Science. 298:2157-2167, 2002.
6. Yoshida, C.A., Furuichi, T., Fujita, T., Fukuyama, R., Kanatani, N., Kobayashi, S., Satake, M., Takada, K. and Komori, T. Core-binding factor _ interacts with Runx2 and is required for skeletal development. Nature Genet. 32:633-638, 2002.
7. Watanabe, T. Nakagawa, K, Ohata, S, Kitagawa, D., Nishitai, G., Seo, J., Tanemura, S., Shimizu, N., Kishimoto, H., Wada, T., Aoki, J., Arai, H., Iwatsubo, T., Mochita, M., Watanabe, T., Satake, M., Ito, Y., Matsuyama, T., Mak, T. W., Penninger, J. M., Nishina, H., and Katada, T. SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kB-induced anti-apoptosis. Dev. Biol. 250:332-347, 2002.
8. Hayashi, K., Abe, N., Watanabe, T., Obinata, M., Ito, M., Sato, T., Habu, S and Satake, M. Overexpression of AML1 transcription factor drives thymocytes into the CD8 single positive lineage. J. Immunol. 167:4957-4965,2001.
9. Yokomizo, T., Ogawa, M., Osato, M., Kanno, T., Yoshida, H., Fujimoto, T., Fraser, S., Nishikawa, S., Okada, H.,Satake, M., Noda, T., Nishikawa, S. and Ito, Y. Requirement of Runx1/AML1/PEBP2aB for the generation of hematopoietic cells from endothelial cells. Genes to Cells, 6:13-23, 2001.
10. Hayashi, K., Natsume, W., Watanabe, T, Abe, N., Iwai, N., Okada, H., Ito, Y., Asano, M., Iwakura, Y., Habu, S., Takahama, Y. and Satake, M. Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single positive T cells. J. Immunol.165:6816-6824, 2000.
11. Takakura, N., Watanabe, T., Suenobu, S., Yamada, Y., Noda, T., Ito, Y., Satake, M. and Suda, T. A role for hematopoietic stem cells in promoting angiogenesis. Cell, 102: 199-209, 2000.
12. Kanto, S., Chiba, N., Tanaka, Y., Fujita, S., Endo, M., Kamada, N., Yoshikawa, K., Fukuzaki, A., Orikasa, S., Watanabe, T. and Satake, M.The PEBP2b/CBFb-SMMHC chimeric protein is localized both in the cell membrane and nuclear subfractions of leukemic cells carrying chromosomal inversion 16. Leukemia, 14: 1253-1259, 2000.
13. Mukouyama, Y., Chiba, N., Hara, T., Okada, H., Ito, Y., Kanamaru, R., Miyajima A., Satake, M. and Watanabe, T. The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region. Develop. Biol. 220: 27-36, 2000.
14. Namba, K., Abe, M., Saito, S., Satake, M., Ohmoto,T., Watanabe, T. and Sato, Y. Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31. Oncogene 19: 106-114, 2000.
15. Mukouyama, Y., Chiba, N., Mucenski, M.L., Satake, M., Miyajima, A., Hara, T. and Watanabe, T. Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb. Current Biol. 9: 833-836, 1999.
16. Okada, H., Watanabe, T., Niki, M., Takano, H., Chiba, N., Yanai, N., Tani, K., Hibino, H., Asano, S., Mucenski, M.L., Ito, Y., Noda, T. and Satake, M. AML1(-/-)embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene 17:2287-2293, 1998.
17. Fujii, M., Hayashi, K., Niki, M., Chiba, N., Meguro, K., Endo, K., Kameoka, J., Ito, S., Abe, K., Watanabe, T. and Satake, M. Overexpression of AML1 renders a T hybridoma resistant to T cell receptor-mediated apoptosis. Oncogene 17:1813-1820, 1998.
18. Tanaka, Y., Fujii, M., Hayashi, K., Chiba, N., Akaishi, T., Shineha, R., Nishihira, T., Satomi, S., Ito, Y., Watanabe, T. and Satake, M. The chimeric protein, PEBP2b/CBFb-SMMHC, disorganizes cytoplasmic stress fibers and inhibits transcriptional activation. Oncogene 17:699-708, 1998.
19. Tanaka, Y., Watanabe, T., Chiba, N., Niki, M., Kuroiwa, Y., Nishihira, T., Satomi, S., Ito, Y. and Satake, M.The protooncogene product, PEBP2b/CBFb, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures. Oncogene 15:677-683, 1997.
20. Chiba, N.,Watanabe, T., Nomura, S., Tanaka, Y., Minowa, M., Niki, M., Kanamaru R. and Satake, M. Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2b/CBFb, in muscle development. Oncogene 14:2543-2552, 1997.
21. Niki, M., Okada, H., Takano, H., Kuno, J., Tani, K., Hibino, H., Asano, S., Ito, Y., Satake, M. and Noda, T. Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, PEBP2/CBF. Proc. Natl. Acad. Sci. USA. 94:5697-5702, 1997.
22. Fujioka, M., Yusibova, G.L., Sackerson, M., Tillib, S., Mazo, A., Satake, M., and Goto, T. Runt domain partner proteins enhance DNA binding and transcriptional repression in cultured Drosophila cells. Genes to Cells 1: 741-754, 1996.