2009 Fiscal Year Final Research Report
Studies on regulatory mechanism for cell migration based on chemical genetics
| Project/Area Number |
19310146
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Keio University |
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Principal Investigator |
IMOTO Masaya Keio University, 理工学部, 教授 (60213253)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Etsu 慶應義塾大学, 理工学部, 講師 (00365446)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 遺伝子 / 癌 / シグナル伝達 |
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| Research Abstract |
UTKO1 was synthesized as a derivative of moverastin by Prof. Watanabe (Univ. Tokyo). We explored the mode of action of UTKO1 by using a chemical genetic approach. We found that UTKO1 inhibited EGF-induced cell migration by inhibiting Rac1 activation. To identify the molecular target of UTKO1, biotinylated UTKO1 was synthesized by Prof. Watanabe, and was used as the probe to obtain a target protein of UTKO1. As a result, 14-3-3ζ was identified as the functional target protein of UTKO1, because siRNA-mediated silencing of 14-3-3ζ expression suppressed both EGF-induced cell migration and Rac1 activation. These results suggest that 14-3-3ζ would act upstream of Rac1 activation in the process of EGF-induced cell migration, and UTKO1 inhibited cell migration possibly due to the abrogation of 14-3-3ζ function.
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[Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase2008
Author(s)
M. Kawatani, H. Okumura, K Honda, N. Kanoh, M. Muroi, N. Dohmae, M. Takami, M. Kitagawa, Y. Futamura, M. Imoto, H. Osada
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Journal Title
I. Proc. Natl. Acad. Sci. U S A 105
Pages: 11691-11696
Peer Reviewed
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[Journal Article] SAR Study of a Novel Triene-ansamycin Group Compound, Quinotrierixin, and Related Compounds, as Inhibitors of ER Stress-induced XBP1 Activation. I. Taxonomy, Fermentation, Isolation, Biological Activities and SAR Study.2008
Author(s)
T. Kawamura, E. Tashiro, K. Yamamoto, K. Shindo, M. Imoto
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Journal Title
J. Antibiot 61
Pages: 303-311
Peer Reviewed
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[Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin.2008
Author(s)
Y. Futamura, R. Sawa, Y. Umezawa, M. Igarashi, H. Nakamura, K. Hasegawa, M. Yamasaki, E. Tashiro, Y. Takahashi, Y. Akamatsu, M. Imoto
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Journal Title
J. Am. Chem. Soc. 130
Pages: 1822-1823
Peer Reviewed
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[Journal Article] Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in hypoxic environment.
Author(s)
M. Takeuchi, S. Kimura, J. Kuroda, E. Ashihara, M. Kawatani, H. Osada, K. Umezawa, E. Yasui, M. Imoto, T. Tsuruo, A. Yokota, R. Tanaka, R. Nagao, T. Nakahata, Y. Fujiyama, T. Maekawa
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Journal Title
Cell Death Diff. (in press)
Peer Reviewed
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