Analysis of physiological function of su l fat i on by regulating the expression of PAPS transporter

• Project/Area Number: 20370051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Soka University
• Principal Investigator: NISHIHARA Shoko Soka University, 工学部・生命情報工学科 (00164575)
• Co-Investigator(Renkei-kenkyūsha): KUDO Takashi 筑波大学, 人間総合科学研究科, 准教授 (20288062) ; TOYODA Hidenao 立命館大学, 薬学部, 教授 (70217579) ; ONO Masaya 国立がんセンター, 化学療法部, 室長 (00270900)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2008: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 糖鎖生物学 / 硫酸化 / PAPs輸送体 / ノックアウトマウス / ES細胞 / RNAi / ノックダウン / 生理機能 / 糖鎖 / 蛋白質 / 発生・分化 / PAPS輸送体

Research Abstract

Sulfation of glycans, lipids, and proteins is involved in a variety of biological phenomena. PAPS transporters (PAPSTs) is a key component of sulfation processes. We performed RNAi knockdown for PAPSTs in mouse ES cells and found that sulfated glycans work on the maintenance and differentiation of ES cells through Wnt, BMP and FGF signals. PAPST1 knockout mice showed that reduction of PAPST activity causes various type of disorders.

Research Products

• [Journal Article] Expression and role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma. (2011)
  • Author(s): Kamiyama S, Ichimiya T, Ikehara Y, Takase T, Fujimoto I, Suda T, Nakamori S, Nakamura M, Nakayama F, Irimura T, Nakanishi H, Watanabe M, Narimatsu N, Nishihara S
  • Journal Title: Glycobiology 21 Pages: 235-246
• [Journal Article] Expression and role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma. (2011)
  • Author(s): Kamiyama, S.
  • Journal Title: Glycobiology Volume: 21 Pages: 235-246
  • Peer Reviewed
• [Journal Article] Gene silencing in mouse embryonic stem cells. (2011)
  • Author(s): Sasaki, N.
  • Journal Title: Methods Mol.Biol. Volume: (in press)
• [Journal Article] Chemical inhibition of sulfation accelerates neural differentiation of mouse embryonic stem cells and human induced pluripotent stem cells. (2010)
  • Author(s): Sasaki N, Hirano T, Kobayashi K, Toyoda M, Miyakawa Y, Okita H, Kiyokawa N, Akutsu H, Umezawa A, Nishihara S
  • Journal Title: BBRC 401 Pages: 480-486
• [Journal Article] Two Golgi-resident 3'-phosphoadenosine 5'-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans. (2010)
  • Author(s): Dejima K, Murata D, Mizuguchi S, Nomura KH, Izumikawa T, Kitagawa H, Gengyo-Ando K, Yoshina S, Ichimiya T, Nishihara S, Mitani S, Nomura K
  • Journal Title: J Biol.Chem. 285 Pages: 24717-24728
• [Journal Article] Two Golgi-resident 3'-phosphoadenosine 5'-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans. (2010)
  • Author(s): Dejima, K.
  • Journal Title: J Biol.Chem. Volume: 285 Pages: 24717-24728
  • Peer Reviewed
• [Journal Article] Chemical inhibition of sulfation accelerates neural differentiation of mouse embryonic stem cells and human induced pluripotent stem cells. (2010)
  • Author(s): Sasaki, N.
  • Journal Title: BBRC Volume: 401 Pages: 480-486
  • Peer Reviewed
• [Journal Article] Glycosyltransferases and transporters that contribute to proteoglycan synthesis in Drosophila : Identification and functional analyses using the heritable and inducible RNAi system. (2010)
  • Author(s): Nishihara, S.
  • Journal Title: Method in Enzymnology Volume: 480 Pages: 323-351
• [Journal Article] The 3'-phosphoadenosine 5'-phosphosulfate transporters, PAPST1 and 2, contribute to the maintenance and differentiation of mouse embryonic stem cells. (2009)
  • Author(s): Sasaki N, Hirano T, Ichimiya T, Wakao M, Hirano K, Kinoshita-Toyoda A, Tovoda H, Suda Y, Nishihara S
  • Journal Title: PLoS One 4
• [Journal Article] The 3'-phosphoadenosine 5'-phosphosulfate transporters, PAPSTI and 2, contribute to the maintenance and differentiation of mouse embryonic stem cells (2009)
  • Author(s): Sasaki, N.
  • Journal Title: PLoS One 4
  • Peer Reviewed
• [Journal Article] The function of glycan structures expressed on embryonicstem cells (2009)
  • Author(s): Nishihara, S.
  • Journal Title: TIGG 21 Pages: 207-218
• [Journal Article] Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells. (2008)
  • Author(s): Sasaki N, Okishio K, Ui-Tei K, Saigo K, Kinoshita-Toyoda A, Tovoda H, Nishimura T, Suda Y, Hayasaka M, Hanaoka K, Hitoshi S, Ikenaka K, Nishihara S
  • Journal Title: J.Biol.Chem. 283 Pages: 3594-3606
• [Journal Article] Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells. (2008)
  • Author(s): Sasaki, N.
  • Journal Title: J. Biol. Chem. 283 Pages: 3594-3606
  • Peer Reviewed
• [Journal Article] Functional analysis of proteoglycan galactosyltransferase II RNAi mutant flies (2008)
  • Author(s): Ueyama, M.
  • Journal Title: J. Biol. Chem. 283 Pages: 6076-6084
  • Peer Reviewed
• [Journal Article] Sequential glycosyltransfer reactions on a microfluidic device : Synthesis of a glycosaminoglycan linkage region tetrasaccharide. (2008)
  • Author(s): Ono, Y.
  • Journal Title: Lab. on a Chip 8 Pages: 2168-2173
  • Peer Reviewed
• [Journal Article] 糖ヌクレオチド輸送体・PAPS輸送体による糖鎖合成の制御. (2008)
  • Author(s): 神山 伸
  • Journal Title: 蛋白質核酸酵素 53 Pages: 1486-1494
• [Journal Article] ES細胞の未分化性、多能性維持に関わる硫酸化糖鎖. (2008)
  • Author(s): 西原祥子
  • Journal Title: 化学工業 59 Pages: 947-954
• [Presentation] 硫酸化阻害剤によるマウスES細胞およびヒトips細胞の神経分化誘導 (2011)
  • Author(s): 小林久美子、佐々木紀彦、平野拓也、豊田雅士、梅澤明弘、西原祥子
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
• [Presentation] 硫酸化阻害剤によるマウスES細胞およびヒトiPS細胞の神経分化誘導 (2011)
  • Author(s): 小林久美子
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
• [Presentation] ES細胞の未分化性・多能性維持、分化シグナルの拠点となる硫酸化糖鎖 (2010)
  • Author(s): 西原祥子、佐々木紀彦、平野和己、隅田泰生、豊田英尚、一宮智美
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)ワークショップ
  • Place of Presentation: 神戸
• [Presentation] Expression and role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma (2010)
  • Author(s): 神山伸、一宮智美、池原譲、中森正二、中村充、中山文明、入村達郎、中西速夫、渡邊昌彦、成松久、西原祥子
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] Functional analysis of sulfated glycans in the differentiation of embryonic stem cells (2010)
  • Author(s): Nishihara S, Sasaki N, Hirano T, Ichimiya T, Hirano K, Toyoda H, Suda Y
  • Organizer: The 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: Makuhari
• [Presentation] Sulfated glycan function in development : from Drosophila to ES cells (2010)
  • Author(s): 西原祥子
  • Organizer: The 8th Naito Conference on Glycan Expression and Regulation [I] Functions and Disease Mechanisms
  • Place of Presentation: Kanagawa
• [Presentation] Sulfation contributes to the maintenance of mouse embryonic stem cells, the differentiation of the embryoid body and the progression of neurogenesis (2010)
  • Author(s): Sasaki N, Hirano T, Ichimiya T, Wakao M, Hirano K, Kinoshita-Toyoda A, Toyoda H, Suda Y, Nishihara S
  • Organizer: 第8回幹細胞シンポジウム
  • Place of Presentation: 淡路
• [Presentation] 硫酸化修飾はES細胞の維持および分化に重要である (2010)
  • Author(s): 佐々木紀彦、平野拓也、一宮智美、平野和己、隅田康生、豊田英尚、西原祥子
  • Organizer: 第9回日本再生医療学会総会
  • Place of Presentation: 広島
• [Presentation] Heparan sulfate contributes to self-renewal and pluripotency in mouse embryonic stem cells (2010)
  • Author(s): Hirano, K.
  • Organizer: 第8回幹細胞シンポジウム
  • Place of Presentation: 淡路
• [Presentation] Sulfated glycan function in development : from Drosophila to ES cells. (2010)
  • Author(s): Nishihara, S.
  • Organizer: The 8th Naito Conference on Glycan Expression and Regulation [I]
  • Place of Presentation: Kanagawa
• [Presentation] Heparan sulfate is required for the maintenance of self-renewal in mouse embryonic stem cells. (2010)
  • Author(s): Hirano, K.
  • Organizer: The 8th Naito Conference on Glycan Expression and Regulation [I]
  • Place of Presentation: Kanagawa
• [Presentation] Functional analysis of sulfation in the maintenance of mouse embryonic stem cells, the differentiation of the embryoid body and the progression of neurogenesis (2010)
  • Author(s): Sasaki, N.
  • Organizer: The 8th Naito Conference on Glycan Expression and Regulation [I]
  • Place of Presentation: Kanagawa
• [Presentation] (2010)
  • Author(s): Nishihara, S.
  • Organizer: The 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: Makuhari
• [Presentation] Expression and role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma (2010)
  • Author(s): 神山伸
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
• [Presentation] ES細胞の未分化性・多能性維持に関わる硫酸化糖鎖 (2009)
  • Author(s): 西原祥子、佐々木紀彦、平野和己
  • Organizer: 第32回日本分子生物学会年会、ワークショップ
  • Place of Presentation: 横浜
• [Presentation] The 3'-phosphoadenosine 5'-phosphosulfate transporters, PAPST1 and PAPST2, are important for the maintenance and the differentiation of mouse embryonic stem cells (2009)
  • Author(s): Nishihara S, Sasaki N, Hirano T, Ichimiya T, Wakao M, Kinoshita-Toyoda A, Tovoda H, Suda Y.
  • Organizer: XX International Symposium on Glycoconjugates
  • Place of Presentation: San Juan (Puerto Rico)
• [Presentation] マウスPAPS輸送体mPAPST1, mPAPST2の機能解析 (2009)
  • Author(s): 幾世高史、一宮智美、藤本泉、尾崎秀徳、工藤墨、中村充、西原祥子
  • Organizer: GlycoTOKYO2009シンポジウム
  • Place of Presentation: 東京
• [Presentation] PAPST1抑制によるBurkittリンパ腫細胞の放射線感受性の増加について (2009)
  • Author(s): 中山文明、梅田禎子、神山伸、一宮智美、西原祥子、明石真言
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] The 3' -phosphoadenosine 5' -phosphosulfate transporters, PAPST1 and PAPST2, are important for the maintenance and the differentiation of mouse embryonic stem cells (2009)
  • Author(s): 西原祥子
  • Organizer: XX International Symposium on Glycoconjugates
  • Place of Presentation: San Juan(Puerto Rico)
• [Presentation] Functional analysis of heparan sulfate in mouse embryonic stemcells (2009)
  • Author(s): Hirano, K.
  • Organizer: The 1^<St> ACGG(Asian Communications of Glycobiology and Glycotechnology)Conference
  • Place of Presentation: 筑波
• [Presentation] Self-renewal and pluripotency of mouse embryonic stem cells are regulated by heparan sulfate, not chondroitin sulfate. (2009)
  • Author(s): Hirano, K.
  • Organizer: Joint Meeting Clinical and Translational Research on Cancer : Glycomics Applications &The 2^<nd>Seminar on Functional Glycomics for Young Investigators
  • Place of Presentation: Mie(Japan)
• [Presentation] Drosophila mutative sugar nucleotide transporter contributes to Dpp signaling. (2009)
  • Author(s): Ueyama, M.
  • Organizer: Joint Meeting Clinical and Translational Research on Cancer : Glycomics Applications &The 2^<nd> Seminar on Functional Glycomics for Young Investigators
  • Place of Presentation: Mie(Japan)
• [Presentation] Heparansulfate regulates self-renewal and pluripotency of embryonic stem cells (2008)
  • Author(s): Sasaki N, Okishio K, Ui-Tei K, Kinoshita-Toyoda A, Toyoda H, Nishimura T., Suda Y, Hayasaka M, Hanaoka K, Nishihara S
  • Organizer: The 23rd Naito Conference on Molecular Basis for Maintenance and Differentiation of Stem Cells
  • Place of Presentation: Kanagawa
• [Presentation] Heparan suliate regulates self-renewal and pluripotency of mouse embryonic stem cells. (2008)
  • Author(s): Nishihara, S.
  • Organizer: The 6th International Symposium on Glycosyltransferases
  • Place of Presentation: Atlanta (USA)
• [Presentation] ヘパラン硫酸はマウス胚性幹細胞の未分化性と多能性を制御する. (2008)
  • Author(s): 佐々木紀彦
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: 筑波
• [Presentation] Heparansulfate regulates self-renewal and pluripotency of embryonic stem cells. (2008)
  • Author(s): Sasaki, N.
  • Organizer: The 23rd Naito Conference on Molecular Basis for Maintenance and Differentiation of Stem Cells
  • Place of Presentation: Kanagawa(Japan)
• [Presentation] Functional analysis of a novel sugar nucleotide transporter candidate gene in Drosophila. (2008)
  • Author(s): Uno, T.
  • Organizer: Annual Conference of the Society for Glyco-biology
  • Place of Presentation: Fort Worth (USA)
• [Presentation] ヘパラン硫酸はマウス胚性幹細胞の未分化性と多能性を制御する. (2008)
  • Author(s): 佐々木紀彦
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2007)ワークショップ
  • Place of Presentation: 神戸
• [Book] The function of glycan structures for the maintenance and differentiation of embryonic stem cells. (2011)
  • Author(s): Nishihara, S.
  • Publisher: INTECH(In press)
• [Book] Method in Enzymnology(480)(Glycosyltransferases and transporters that contribute to proteoglycan synthesis in Drosophila : Identification and functional analyses using the heritable and inducible RNAi system.) (2010)
  • Author(s): 西原祥子
• [Book] The function of glycan structures expressed on embryonic stem cells. (2009)
  • Author(s): 西原祥子
  • Publisher: TIGG(21)
• [Book] 化学工業(59)(ES細胞の未分化性、多能性維持に関わる硫酸化糖鎖) (2008)
  • Author(s): 西原祥子
• [Book] 蛋白質核酸酵素(53)(糖ヌクレオチド輸送体・PAPS輸送体による糖鎖合成の制御) (2008)
  • Author(s): 神山伸、西原祥子
• [Book] Experimental Glycoscience-Glycobiology(edited by Naoyuki Taniguchi et al.)(Nucleotide sugar transporter genes and their functional analysis.) (2008)
  • Author(s): 西原祥子
  • Publisher: Springer(Partl, Section III)
• [Book] Nucleotide sugar transporter genes and their functional analysis. (2008)
  • Author(s): Nishihara, S.
  • Publisher: Experimental Glycoscience-Glycobiology, edited by Naoyuki Taniguchi et al., Springer, Parti, Section III
• [Book] Embryonic Stem Cells(The function of glycan structures for the maintenance and differentiation of embryonic stem cells.)
  • Author(s): 西原祥子
  • Publisher: INTECH(in press)
• [Book] Methods Mol. Biol.(Gene silencing in mouse embryonic stem cells.)
  • Author(s): Sasaki N, Nishihara S
  • Publisher: (in press.)
• [Remarks] ホームページ等
  • URL: http://www.t.soka.ac.jp/menu/grad/grad_bio/grad_prof_bio/mc_bio02/grad_s_nishihara.html
• [Patent(Industrial Property Rights)] 胚様体分化制御剤 (2010)
  • Inventor(s): 西原祥子、佐々木紀彦
  • Industrial Property Rights Holder: 西原祥子、佐々木紀彦
  • Industrial Property Number: 2010-261170
  • Filing Date: 2010-11-24
• [Patent(Industrial Property Rights)] 神経細胞の製造方法及び神経細胞分化促進剤 (2010)
  • Inventor(s): 西原祥子、佐々木紀彦
  • Industrial Property Rights Holder: 西原祥子、佐々木紀彦
  • Industrial Property Number: 2010-223472
  • Filing Date: 2010-10-01
• [Patent(Industrial Property Rights)] 分化制御剤、分化抑制基材及び分化抑制方法並びにその使用 (2010)
  • Inventor(s): 西原祥子、佐々木紀彦
  • Industrial Property Rights Holder: 西原祥子、佐々木紀彦
  • Industrial Property Number: 2008-167493
  • Filing Date: 2010-06-26
• [Patent(Industrial Property Rights)] 胚様体分化制御剤 (2009)
  • Inventor(s): 西原祥子、佐々木紀彦
  • Industrial Property Rights Holder: 西原祥子、佐々木紀彦
  • Industrial Property Number: 2009-267231
  • Filing Date: 2009-11-25
• [Patent(Industrial Property Rights)] 胚様体分化制御剤 (2009)
  • Inventor(s): 西原祥子, 佐々木紀彦
  • Industrial Property Rights Holder: 学校法人創価大学、タマティーエルオー株式会社
  • Industrial Property Number: 2009-267231
  • Filing Date: 2009-11-25
• [Patent(Industrial Property Rights)] 分化制御剤、分化抑制基材及び分化抑制方法並びにその使用 (2008)
  • Inventor(s): 西原祥子, 佐々木紀彦
  • Industrial Property Rights Holder: 出願人 : 学校法人創価大学, タマティーエルオー株式会社
  • Industrial Property Number: 2008-167493
  • Filing Date: 2008-06-26