Golgi stress response by proteoglycans

• Project/Area Number: 24659039
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: KITAGAWA Hiroshi 神戸薬科大学, 薬学部, 教授 (40221915)
• Co-Investigator(Renkei-kenkyūsha): NADANAKA Satomi 神戸薬科大学, 薬学部, 講師 (60378578)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プロテオグリカン / 糖転移酵素 / 硫酸化糖鎖 / ノックアウトマウス / ガン抑制遺伝子 / ストレス応答 / リン酸化 / 脱リン酸化 / 癌抑制遺伝子 / ゴルジ体

Research Abstract

Glycosaminoglycans (GAGs) are components of proteoglycans (PGs), which are abundant on the surfaces of most cells and in extracellular matrices. PGs are known to function as cofactors in a variety of biological processes. Most biological activities of PGs are attributed to the GAG side chains that interact with diverse protein ligands via specific saccharide sequences. EXTL2, a member of the EXT family of tumor suppressors, functions to suppress any GAG biosynthesis that is enhanced by a xylose kinase, and thus lack of EXTL2 causes GAG overproduction and structural changes to GAGs. These poor-quality GAGs have effects on the cell signaling such as HGF-mediated and BMP-mediated signaling, and consequently disturb liver regeneration and blood vessel remodeling. Therefore, the EXTL2-dependent mechanism that regulates GAG biosynthesis might be a "quality control system" for PGs and GAGs produced in the absence of EXTL2 can be closely associated with diseases.

Research Products

• [Journal Article] EXTL2 controls liver regeneration and aortic calcification through xylose kinase-dependent regulation of glycosaminoglycan biosynthesis (2013)
  • Author(s): Nadanaka, S., Kitagawa, H.
  • Journal Title: Matrix Biol Volume: 35 Pages: 18-24
  • Peer Reviewed
• [Journal Article] Glycosaminoglycan Overproduction in the Aorta Increases Aortic Calcification in Murine Chronic Kidney Disease. (2013)
  • Author(s): Purnomo E, Emoto N, Nugrahaningsih DAA, Nakayama K, Yagi K, Heiden S, Nadanaka S, Kitagawa H, Hirata KI.
  • Journal Title: JAHA Volume: 2 Issue: 5
  • DOI: 10.1161/jaha.113.000405
  • Peer Reviewed
• [Journal Article] Roles of EXTL2, a member of EXT family of tumor suppressors, in liver injury and regeneration processes. (2013)
  • Author(s): Nadanaka, S., Kagiyama, S., and Kitagawa, H.
  • Journal Title: Biochem. J. Volume: 454 Issue: 1 Pages: 133-145
  • DOI: 10.1042/bj20130323
  • Peer Reviewed
• [Journal Article] EXTL2, a member of EXT family of tumor suppressors, controls glycosaminoglycan biosynthesis in a xylose kinase-dependent manner (2013)
  • Author(s): Nadanaka, S., Zhou, S., Kagiyama, S., Shoji, N., Sugahara, K., Sugihara, K., Asano, M.and Kitagawa, H.
  • Journal Title: J. Biol. Chem Volume: 288 Issue: 13 Pages: 9321-9333
  • DOI: 10.1074/jbc.m112.416909
  • Peer Reviewed
• [Journal Article] Glycosaminoglycan overproduction in the aorta increases aortic calcification in murine chronic kidney disease. (2013)
  • Author(s): Purunomo, E., Emoto, N., Nugrahaningsih, D., Nakayama, K., Yagi, K., Heiden, S., Nadanaka, S., Kitagawa, H., and Hirata, K.
  • Journal Title: J. Am. Heart Assoc. Volume: 2
  • Peer Reviewed
• [Presentation] プロテオグリカン研究の魅力〜細胞の分化を制御するコンドロイチン硫酸〜 (2013)
  • Author(s): 北川裕之
  • Organizer: H25年度生理学研究所研究会「構造の多様性に立脚した糖鎖機能の解明に向けて」
  • Place of Presentation: 岡崎
  • Year and Date: 2013-11-14
• [Presentation] 糖鎖リモデリングによるコンドロイチン硫酸の機能解析 (2013)
  • Author(s): 北川裕之
  • Organizer: 第64回FCCAセミナー/FCCAグライコサイエンス若手フォーラム2013
  • Place of Presentation: 大阪
  • Year and Date: 2013-08-08
• [Presentation] EXTL2によるグリコサミノグリカン合成調節機構とその破綻による急性肝炎の重篤化 (2013)
  • Author(s): 灘中里美,Shaobo Zhou,鍵山正二,庄司奈緒子,菅原一幸,杉浦一司,浅野雅秀,北川裕之
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪
• [Presentation] EXTL２によるグリコサミノグリカン合成調節機構とその破綻による急性肝炎の重篤化 (2013)
  • Author(s): 灘中 里美，Shaobo Zhou, 鍵山 正二，庄司 奈緒子，菅原 一幸，杉浦 一司，浅野 雅秀，北川 裕之
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪
• [Presentation] Altered cell surface heparan sulfate expressions induce osteoblastic differentiation and attenuate phagocytosis activity of human coronary artery smooth muscle cells (HCASMCs) (2012)
  • Author(s): Purnomo, E., Emoto, N., Nugrahaningsih, D. A. A., Yagi, K., Nakayama, K., Nadanaka, S., Kitagawa, H., Hirata, K.
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
• [Presentation] 糖鎖リモデリングによるコンドロイチン硫酸の機能解析
  • Author(s): 北川 裕之
  • Organizer: 第64回FCCAセミナー /FCCAグライコサイエンス若手フォーラム2013
  • Place of Presentation: 大阪
  • Invited
• [Presentation] H25年度 生理学研究所研究会 「構造の多様性に立脚した糖鎖機能の解明に向けて」
  • Author(s): 北川 裕之
  • Organizer: プロテオグリカン研究の魅力～細胞の分化を制御するコンドロイチン硫酸
  • Place of Presentation: 岡崎
  • Invited
• [Book] Exostosin (multiple)-like 1-3 (EXTL1-3). Handbook of Glycosyltransferases and Related Genes, 2nd Ed (2014)
  • Author(s): Nadanaka, S., Kitagawa, H.(Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., and Angata, T., eds)
  • Publisher: Springer (in press)
• [Remarks]
  • URL: http://www.kobepharma-u.ac.jp/~biochem/
• [Remarks] 神戸薬科大学 生化学研究室
  • URL: http://www.kobepharma-u.ac.jp/~biochem/
• [Remarks] 神戸薬科大学 生化学研究室
  • URL: http://www.kobepharma-u.ac.jp/~biochem/