Yoshinori Akiyama, D. Sci, Professor
Our research projects are concerned with post-translational events in the expression of genetic information. Specifically, processes of protein translocation across and integration into the membrane, membrane protein proteolysis and extracytoplasmic stress responses are investigated by combined molecular genetic, biochemical and structural approaches. Second group is studying the lifecycle of HPV and the molecular mechanism of the virus-induced tumor formation. The interaction between HIV and host immune cells is also under investigation. Third group is studying the regulatory mechanism of Wnt/β-catenin pathway and its role on cell biology.
Research and EducationProtein translocation across the membrane is mediated by the evolutionary conserved SecYEG complex, the motor protein SecA and the accessory membrane complex SecDF in Bacteria. We are trying to elucidate the molecular mechanism of this process.
Proteolysis plays important roles not only in quality control but also in functional regulation of membrane proteins. We are interested in both of these aspects. Also we address the problem of how an E coli cell responds to the cell surface stresses caused by accumulation of abnormal membrane proteins.
HPV infection and the tumorigenesis: The HPV replication is strictly regulated by the differentiation program of the host cell. We are investigating the cross-talk between the virus and the host cell.
Regulatory mechanism of Wnt/β -catenin pathway: I found that overexpression of Keratin associated protein (Krtap) 13 markedly stimulates Wnt signaling. I generated a Krtap13-transgenic mouse system that enable to analyze effect of tissue specific overexpression of Krtap13 in vivo.
Fig. 1: Translocation/integration, folding, and degradation of the E. coli cell surface proteins and cellular responses to membrane stresses.
Fig. 2:Ras activation conferred invasion potential to keratinocytes expressing high-risk type E7.
- Akiyama, K.a, Mizuno, S.a, Hizukuri, Y., Mori, H., Nogi, T., and Akiyama, Y. (2015) Role of membrane-reentrant β-hairpin-like loop of RseP protease in selective substrate cleavage. eLife e08928. a equally contributed
- Ishii, E., Chiba, S., Hashimoto, N., Kojima, K., Homma, M., Ito, K., Akiyama, Y., and Mori, H. (2015) Nascent chain-monitored remodeling of the Sec machinery for salinity adaptation of marine bacteria. Proc. Natl. Acad. Sci. USA 112, E5513–E5522.
- Narita, S.-i., Masui, C., Suzuki, T., Dohmae, N., and Akiyama, Y. (2013) Protease homolog BepA (YfgC) promotes assembly and degradation of β-barrel membrane proteins in Escherichia coli. Proc. Natl. Acad. Sci. USA 110, E3612–E3621
- Ueno, T., Sasaki, K., Yoshida, S., Kajitani, N., Satsuka, A., Nakamura, H. and Sakai, H. (2006) Molecular mechanisms of hyperplasia induction by human papillomavirus E7. Oncogene 25, 4155-4164
- Ma, G., Yasunaga, J.-I., Fan, J., Yanagawa, S.-I., Matsuoka, M. (2012) HTLV-1bZIP factor dysregulates the Wnt pathways to support proliferation and migration of adult T-cell leukemia cells. Oncogene 32, 4222-4230
LaboratoryProfessor： Yoshinori Akiyama
Associate professor： Hiroyuki Sakai, Hiroyuki Mori
Assistant professor： Shin-ichi Yanagawa, Yohei Hizukuri