The 21st Century Center of Excellence Program

The Project Leader's Profile

Tadashi Suzuki (Ph.D.)
Visiting Associate Professor, Osaka University Medical School/ Graduate School of Medicine

Graduated from the Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo in 1992. Obtained a Ph.D. degree in 1997. From 1997-2000 he was a post-doctoral fellow at the Department of Biochemistry and Cell Biology, State University of New York at Stony Brook. During this period he was a JSPS (Japan Society for the Promotion of Science) pre/postdoctoral
fellow for young researchers (1996-1998) and JSPS oversea research fellow (1998-2000). In 2000, he was appointed as a Research Assistant Professor. From December 2001, he serves as a researcher of the Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Corporation (JST). From February 2002 he was also an RCF Assistant Professor at the Undergraduate Program for Bioinformatics and Systems Biology (UPBSB), Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo. From January 2004, he is appointed as a visiting associate professor at Osaka University Graduate School of Medicine.

Project Leader:	Tadashi Suzuki, Ph.D., Visiting Associate Professor, Osaka University Medical School/ Graduate School of Medicine
Research Collaborators:	Yoko Funakoshi, Ph. D., Japan Science and Technology Agency Kaori Tanabe, Ph. D., Post-doctoral fellow of the 21st Century COE Program of Department of Biochemistry, Osaka University Medical School / Graduate School of Medicine.

Peptide:N-glycanase (PNGase) cleaves asparagine-linked (N-linked) glycan from glycoproteins. Recent studies have shown that this enzyme is involved in quality contol system for newly synthesized glycoproteins in the endoplasmic reticulum (ER). This quality control system distinguishes normal proteins from misfolded and/or unassembled proteins, that are to be degraded by the mechanism called "ER-associated degradation" (ERAD). There is growing evidence that impairment the ERAD function in mammals results in various inherited/acquired neurodegenerative diseases.
We have discovered, purified the cytoplasmic PNGase and subsequently cloned the gene encoding this enzyme. Currently our focus is to analyze structure and function of a newly-found protein complex that involves the cytoplasmic PNGase. It is interesting to note that, while the monocellular organisms such as budding yeast exhibit little effects upon defect of this enzyme, multicellular organisms showed distinct phenotypes such as abnormal axon branching. We therefore aim to unveil the precise role of PNGase, defect of which causes such pivotal phenotypic consequences. Especially we are interested in how these phenotypes are related to its functional importance in ERAD process.
Occurrence of free N-linked glycan released by PNGase has been known for years. It has been demonstrated in plants that free N-glycans has a hormone-like activity promoting growth and ripening of fruits. Moreover, in mammalian cells extensive biochemical studies revealed the very sophisticated intracellular transport/processing pathway of free N-glycan. However, in either case the molecular mechanism of this process remains largely unknown. For instance, recently the cytoplasmic PNGase was found to play a major role for generating the free N-glycan in the cytosol of budding yeast, while it was also shown that there are still unidentified, PNGase-independent pathway to form free N-glycans.
Most recently we have succeeded in cloning the gene encoding the cytoplasmic endo-β-N-acetylglucosaminidase (ENGase), which has been thought to be involved in the critical step for the processing of free N-glycan in the cytosol. This finding will lead to the better understanding of processing of free N-glycans, which is still enigmatic even in this "post-genome" era. In the future we'd like to figure out the whole picture of formation, modification and transport of free N-glycans by identifying molecules involved. The molecular identification of proteins that involved in this process will enable us to assess its functional significance.

1）	Suzuki T, Hara I, Nakano M, Zhao G, Lennarz WJ, Schindelin H, Taniguchi N, Totani K, Matsuo I, and Ito Y. Site-specific labeling of cytoplasmic peptide:N-glycanase by N,N’-diacetylchitobiose-related compounds. J. Biol. Chem., 281, 22152-22160, 2006.
2)	Suzuki T, Hara I, Nakano M, Shigeta M, Nakagawa T, Kondo A, Funakoshi Y, and Taniguchi N. Man2C1, an α-mannosidase is involved in the trimming of free oligosaccharides in the cytosol. Biochem. J., 400, 33-41, 2006.
3)	Suzuki T, Park H, Kwofie MA, and Lennarz WJ. Rad23 provides a link between the Png1 Deglycosylating Enzyme and the 26S Proteasome in Yeast. J. Biol. Chem., 276, 21601-21607, 2006.
4)	Suzuki T, Park H, Hollingsworth NM, Sternglanz R, and Lennarz WJ. PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase. J. Cell Biol., 149, 1039-1051, 2006.
5)	Suzuki T, Yano K, Sugimoto S, Kitajima K, Lennarz WJ, Inoue S, Inoue Y, and Emori Y. Endo-β-N-acetylglucosaminidase, an enzyme involved in the processing of free oligosaccharides in the cytosol. Proc. Natl. Acad. Sci. USA., 99, 9691-9696, 2002.