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. Third group is studying the regulatory mechanism of Wnt/b-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. Vibrio VemP acts to regulate expression of the down stream SecDF genes through its translational elongation arrest.
Proteolysis plays important roles not only in quality control but also in functional regulation of membrane proteins. We are interested in both 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/b-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: Protein translocation/integration (left), extracytoplasmic stress response (center), and surface protein degradation (right) in Gram-negative bacteria.
Fig. 2: Ras activation conferred invasion potential to keratinocytes expressing high-risk type E7.
- Shahrizal, M., Daimon, Y., Tanaka, Y., Hayashi, Y., Nakayama, S., Iwaki, S., Narita, S., Kamikubo, H., Akiyama, Y., and Tsukazaki, T. (2019) Structural basis of the function of the β-barrel assembly-enhancing protease BepA. J. Mol. Biol. 431, 625-635.
- Mori, H., Sakashita, S., Ito, J., Ishii, E., and Akiyama, Y. (2018) Identification and characterization of a translation arrest motif in VemP by systematic mutational analysis. J. Biol. Chem. 293, 2915-2926.
- Miyazaki, R., Myougo, N., Mori, H., and Akiyama, Y. (2018) A photo-cross-linking approach to monitor folding and assembly of newly synthesized proteins in a living cell. J. Biol. Chem. 293, 677-686.
- 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 Oct8. doi: 10.1038/onc.2012.450
Associate professor：Hiroyuki Sakai, Hiroyuki Mori
Assistant professor：Shin-ichi Yanagawa, Yohei Hizukuri