亀村 和生（かめむら・かずお）
Kazuo Kamemura
職位：講師
学位：博士（学術）（三重大学）
●三重大学大学院生物資源学研究科博士課程修了
●科学技術振興機構、日本学術振興会、理化学研究所の研究員を経て本学へ
専門分野
細胞制御学、糖鎖生物学
研究テーマ
細胞分化や増殖制御に関わる未知のタンパク質複合体の機能や分子ネットワークの調節機構（翻訳後修飾）を解明し、生命システムの理解に貢献するとともに、メタボリック・シンドロームや癌などの新規標的分子を同定することを目標にしています。
（1）細胞分化とO-GlcNAc修飾
リン酸化カスケードによる細胞内情報伝達システムに拮抗、あるいは協調する翻訳後修飾 'O-GlcNAc' に注目し、間葉系細胞の新規分化制御メカニズムの解明を行っています。
（2）アポトーシスとO-GlcNAc修飾
O-GlcNAc修飾に注目し、アポトーシス実行過程で起こるエネルギー依存的な核断片化やイートミーシグナルの提示などの新規制御メカニズムの解明を行っています。
（3）細胞増殖調節因子のアセチル化と細胞がん化
エピジェネシス制御の主要な鍵因子、ヒストン脱アセチル化酵素（HDAC）のなかには、サイトゾルで活性を発揮する異色の分子があります。HDAC6は、サイトゾルでチューブリン、HSP90、コータクチンなどに働きかけ、種々の細胞現象を操るHDACです。HDAC6が関わる細胞現象の解明を行っています。
Topics of research
Most of the protein functions are precisely regulated by post-translational modifications (PTMs) in vivo. Especially, the physiological/pathological significance of PTM has been becoming evident according as the progress in epigenetic research.
Although more than two hundreds of PTMs have been discovered, most of their biological roles still await unraveling. Among PTMs, I am focusing my study on the two kinds of the nucleo-cytoplasmic PTMs, glycosylation (O-GlcNAc) and acetylation.
1. Physiological role of O-GlcNAc in mesenchymal cell differentiation
O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous and abundant post-translational modification found on nucleocytoplasmic proteins in multicellular organisms studied so far. O-GlcNAcylation is essential for mouse ES cell viability and development, and is thought to be required in a tissue-specific manner at later stage. Since aberrant O-GlcNAcylation has a link with insulin resistance, it is important to establish the role of O-GlcNAc in differentiation of mesenchymal cells such as preadipocytes and myoblasts. Differentiation-specific O-GlcNAcylation of these cells are biochemically studied.
2. A new O-GlcNAc-mediated signaling in apoptosis
Cycling of O-GlcNAc is regulated by two highly conserved enzymes, O-GlcNAc transferase and cytosolic β-N-acetylglucosaminidase (O-GlcNAcase). O-GlcNAcase is a substrate for caspase-3 in vivo. O-GlcNAcase activity keeps after cleavage by caspase-3, indicating that O-GlcNAcylation has a role for apoptotic process. To gain insight for the functional significance of O-GlcNAc during apoptosis, O-GlcNAcylation specific for apoptotic process is investigated.
3. Impact of cytoplasmic 'non-histone' protein acetylation on cellular events
Histone deacetylase 6 (HDAC6) is a cytoplasmic protein deacetylase that associates with microtubules and deacetylates α-tubulin. HSP90 and cortactin are another known substrates of HDAC6. By deacetylating these substrates, HDAC6 modulates a wide variety of cellular events such as endosome trafficking. To unveil another side of HDAC6, effect of HDAC6-mediated protein deacetylation on mitochondrial function is focused.
主な業績論文等
- K. Kamemura, A. Ito, T. Shimazu, A. Matsuyama, S. Maeda, T-P. Yao, S. Horinouchi, S. Khochbin, and M. Yoshida. Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells. Biochem. Biophys. Res. Commun., 374, 84-89 (2008).
- K. Iemura, K. Kamemura, and M. Miwa. Assessment of the centrosome amplification by quantification of γ-tubulin in Western blotting. Anal. Biochem., 371, 256-258 (2007).
- K. Kamemura and G. W. Hart. Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: A new paradigm for metabolic control of signal transduction and transcription. Prog. Nucleic Acid Res. Mol. Biol., 73, 107-136 (2003).
- K. Kamemura, B. K. Hayes, F. I. Comer, and G. W. Hart. Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: alternative glycosylation/phosphorylation of Thr-58, a known mutational hot spot of c-Myc in lymphomas, is regulated by mitogens. J. Biol. Chem., 277, 19229-19235 (2002).
