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研究活動

教員の紹介(亀村 和生)

バイオサイエンス学科

亀村 和生(かめむら・かずお)
Kazuo Kamemura

専門分野/細胞制御学、糖鎖生物学
研究キーワード/細胞分化、神経変性、がん遺伝子産物、分子標的化合物

職位:准教授
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

研究室紹介
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研究テーマ
 細胞分化や増殖制御に関わるタンパク質複合体の分子構造や機能、細胞内のタンパク質分子ネットワークの翻訳後修飾による調節機構を解明し、生命システムの理解に貢献するとともに、癌・神経変性疾患やメタボリック・シンドロームなどの予防・治療のための新規ターゲットを同定することを目標にしています。
 特に、リン酸化カスケードによる細胞内情報伝達システムや、エピジェネティクスに関与する翻訳後修飾 ‘O-GlcNAc’ に注目しています。

(1) 細胞分化・がん化とO-GlcNAc修飾

 間葉系幹細胞等の新規分化制御メカニズムの解明を行っています。また、がん遺伝子産物に焦点を当て、O-GlcNAc 修飾による機能制御メカニズムを追究しています。

(2) 神経変性疾患の原因タンパク質に起こるO-GlcNAc修飾

 アルツハイマー病や前頭側頭葉変性症などの神経変性疾患の原因タンパク質に起こるO-GlcNAc 修飾に注目し、異常封入体形成メカニズムを追究しています。

研究の応用領域 産官学連携で求めるパートナー
新しい治療薬・診断薬やサプリメントの開発への応用が期待できます。 動物生理学、天然物化学など異分野の研究者、上記の応用領域の展開を望まれる企業や自治体の方々。
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 unveiling. Among PTMs, we are focusing on the two kinds of the nucleo-cytoplasmic PTMs, glycosylation( O-GlcNAc) and phosphorylation.

(1) O-GlcNAc in mesenchymal cell differentiation
O-linkedβ-N-acetylglucosaminylation( O-GlcNAcylation) is a ubiquitous and abundant post-translational modification found on nucleocytoplasmic proteins in multicellular organisms. 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 preosteoblasts, preadipocytes and myoblasts. Differentiation-specific O-GlcNAcylation of these cells is biochemically being studied.

(2) O-GlcNAcylation of Ewing’s sarcoma proto-oncoprotein
Although Ewing’s sarcoma protein( EWS) is involved in DNA recombination & repair, transcription, and RNA processing, the precise function of EWS is still unknown. Chimeric EWS oncoprotein generated by chromosomal translocations between EWSR1 and an ETS transcription factor cause malignant tumors. To understand the loss of function of the intact EWS by the translocations, the biological role of the intact EWS should be clarified. EWS is a known O-GlcNAcylated protein. To gain insight into the functional significance of the intact EWS, the biological function of O-GlcNAcylation of EWS is being studied.

(3) Post-translational modifications of the FET proteins
Of the FET( FUS/EWS/TAF15) protein family, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. Based on this circumstantial evidence, the regulatory mechanism of EWS to form fibrous assemblies seems to be distinct from that of the other FET proteins. It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. The effect of PTMs on the fibrous assemblies of FET proteins is being studied.

主な業績論文等
  1. Kamemura, K. O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry. Biosci. Biotechnol. Biochem. 81, 541-546 (2017)
  2. Kamemura, K., Abe H. The glycosylation stoichiometry of EWS species in neuronal cells. Biosci. Biotechnol. Biochem. 81, 165-167 (2017)
  3. Ogawa, M., Sawaguchi, S., Kamemura, K., Okajima T. Intracellular and extracellular O-linked N-acetylglucosamine in the nervous system. Exp. Neurol. 274, 166-174 (2015)
  4. Koyama T., Kamemura K. Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation. Exp. Cell Res. 338, 194-202 (2015)
  5. Li, Q., Kamemura, K. Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells. Biochem. Biophys. Res. Commun. 450, 588-592 (2014)