Yamaguchi University School of Medicine

Departement of Biochemistry and Molecular Biology

Research Activities

Aims of our researches are to understand molecular mechanisms of heat shock response and physiological roles of heat shock transcription factors. By generating chicken B lymphocyte DT40 cells deficient for HSF1 and HSF3, we have shown mechanisms of how heat shock transcription factors support cell survival against detrimental effects of various stresses. HSFs regulate heat shock genes, and also other anti-apoptotic genes. Furthermore, we showed that HSF1 promotes male germ cell death when these cells are exposed to a thermal stress. This observation suggests HSF1 also activate expression of pro-apoptotic genes in adition to anti-apoptotic heat shock genes. Furthermore, we recently generated HSF1-null and HSF4-null mice. Analysis of these mice revealed developmental abnormalities such as cataract, indicating that HSFs are essential for development. We are now on the way to analyze developmental roles of HSFs.

Selected Publications

1. M. Fujimoto, H. Izu, K. Seki, K. Fukuda, T. Nishida, S. Yamada, K. Kato, S. Yonemura, S. Inouye, and A. Nakai. (2004) HSF4 is required for normal cell growth and differentiation during mouse lens development. EMBO J., in press.

2. S. Inouye, H. Izu, E. Takaki, H. Suzuki, M. Shirai, Y. Yokota, H. Ichikawa, M. Fujimoto, A. Nakai. (2004) Impaired IgG production in mice deficient for heat shock transcription factor 1. J. Biol. Chem. 279, 38701-38709.

3. S. Inouye, K. Katsuki, H. Izu, M. Fujimoto, K. Sugahara, S. Yamada, Y. Shinkai, Y. Oka, Y. Katoh, A. Nakai. (2003) Activation of heat shock genes is not necessary for heat shock transcription factor 1 to protect cell death against a single exposure to high temperatures. Mol. Cell. Biol. 23: 5882-5895.

4. A. Nakai, T. Ishikawa. (2001) Cell cycle transition under stress conditions controlled by vertebrate heat shock factors. EMBO J. 20: 2885-2895.

5. A. Nakai, M. Suzuki, M. Tanabe. (2000) Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1. EMBO J. 19: 1545-1554.

6. M. Tanabe, Y. Kawazoe, S. Takeda, R. I. Morimoto, K. Nagata A. (1998) Nakai. Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance. EMBO J. 17: 1750-1758.

Contact Information

Akira Nakai, MD&PhD

Professor, Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan

Phone: 0836-22-2214 Fax 0836-22-2315 E-mail: anakai@yamaguchi-u.ac.jp