Search for the intracellular substrates and activators of coagulation factor XIII (plasma transglutaminase)

• Project/Area Number: 25460379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Yamagata University
• Principal Investigator: SOURI Masayoshi 山形大学, 医学部, 准教授 (20292419)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 酵素 / トランスグルタミナーゼ / 凝固第XIII因子 / 細胞内基質 / 細胞内活性化 / タンパク質架橋結合 / 巨核球 / 単球 / 細胞核 / 分化・成熟

Outline of Final Research Achievements

The A subunit of coagulation factor XIII (FXIII-A) is a plasma transglutanimase (TGase), which exists not only in plasma but also inside bone marrow-derived cells such as megakaryocytes and monocytes/macrophages. In the present study, we examined the intracellular activation and activity of FXIII-A. We found that there was an activation factor(s) of FXIII-A in nucleus in the absence of proteolytic cleavage of the activation peptide in FXIII-A, and that at least three nuclear proteins were identified as possible substrates for FXIII-A. Furthermore, our study suggested that amine-modification of proteins by TGase activity regulates functions of the substrate proteins by the acceleration of proteasomal degradation in the absence of ubiquitination.

Research Products

• [Journal Article] The non-catalytic B subunit of coagulation factor XIII accelerates fibrin cross-linking. (2015)
  • Author(s): Souri M, Osaki T, Ichinose A.
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 19 Pages: 12027-12039
  • DOI: 10.1074/jbc.m114.608570
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anti-factor XIII A subunit (FXIII-A) autoantibodies block FXIII-A2B2 assembly and steal FXIII-A from native FXIII-A2B2. (2015)
  • Author(s): Souri M, Osaki T, Ichinose A.
  • Journal Title: Journal of Thrombosis and Haemostasis Volume: 13 Issue: 5 Pages: 802-814
  • DOI: 10.1111/jth.12877
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Severe congenital factor XIII deficiency caused by novel W187X and G273V mutations in the F13A gene; diagnosis and classification according to the ISTH/SSC guidelines. (2014)
  • Author(s): Souri M, Biswas A, Misawa M, Omura H, Ichinose A.
  • Journal Title: Haemophilia. Volume: 20 Issue: 2 Pages: 255-262
  • DOI: 10.1111/hae.12298
  • Peer Reviewed
• [Journal Article] Clot retraction is mediated by factor XIII-dependent fibrin-aIIbb3-myosin axis in platelet sphingomyelin-rich membrane rafts (2013)
  • Author(s): Kasahara, K., Kaneda, M., Miki, T., Iida, K., Sekino-Suzuki, N., Kawashima, I., Suzuki, H., Shimonaka, M., Arai, M., Ohni-Iwashita, Y., Kojima, S., Abe, M., Kobayashi, T., Okazaki, T., Souri, M., Ichinose, A., Yamamoto, N.
  • Journal Title: Blood Volume: 122(19) Issue: 19 Pages: 3340-3348
  • DOI: 10.1182/blood-2013-04-491290
  • Peer Reviewed
• [Journal Article] 慢性炎症性腸疾患と第XIII(13)因子． (2013)
  • Author(s): 惣宇利正善, 一瀬白帝
  • Journal Title: 別冊BIO Clinica 慢性炎症と疾患 骨髄―末梢血による炎症の制御と修飾 Volume: 2 Pages: 28-33
• [Presentation] 非酵素部位である凝固第XIII因子Bサブユニットのフィブリン架橋反応における見過ごされていた役割 (2015)
  • Author(s): 惣宇利正善、尾崎 司、一瀬白帝
  • Organizer: 第38回日本分子生物学会・第88回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド（神戸）
  • Year and Date: 2015-12-02
• [Presentation] 後天13における抗F13自己抗体の特徴． (2015)
  • Author(s): 惣宇利正善，尾崎 司，一瀬白帝
  • Organizer: 北日本後天性血友病診療ネットワーク学術集会
  • Place of Presentation: キャンパス・イノベーションセンター（東京）
  • Year and Date: 2015-03-08
• [Presentation] フィブリン架橋反応における抗XIII因子自己抗体の阻害作用機序． (2014)
  • Author(s): 惣宇利正善，尾崎 司，一瀬白帝
  • Organizer: 第22回山形分子生物学セミナー
  • Place of Presentation: 山形大学小白川キャンパス（山形）
  • Year and Date: 2014-11-08
• [Presentation] Characterization of plasma pro-transglutaminase, coagulation factor XIII, using its synthetic peptides． (2014)
  • Author(s): 尾崎 司，惣宇利正善，一瀬白帝
  • Organizer: 第22回山形分子生物学セミナー
  • Place of Presentation: 山形大学小白川キャンパス（山形）
  • Year and Date: 2014-11-08
• [Presentation] 先天性凝固第XIII因子Bサブユニット欠損症例に生じた抗Bサブユニット同種抗体による活性阻害． (2014)
  • Author(s): 惣宇利正善，尾崎 司，和田秀穂，一瀬白帝
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Characterization of plasma pro-transglutaminase, coagulation factor XIII, using its synthetic peptides. (2014)
  • Author(s): 尾崎 司，惣宇利正善，一瀬白帝
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 先天性凝固第XIII因子Bサブユニット欠損症例に生じた抗Bサブユニット同種抗体による活性阻害． (2014)
  • Author(s): 惣宇利正善，尾崎 司，和田秀穂，一瀬白帝
  • Organizer: 第17回トランスグルタミナーゼ研究会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-14
• [Presentation] Characterization of plasma pro-transglutaminase, coagulation factor XIII, using its synthetic peptides. (2014)
  • Author(s): 尾崎 司，惣宇利正善，一瀬白帝
  • Organizer: 第17回トランスグルタミナーゼ研究会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-14
• [Presentation] 凝固XIII因子インヒビターの鋭敏な検出のための新規XIII因子活性測定法の開発． (2014)
  • Author(s): 惣宇利正善，尾崎 司，一瀬白帝
  • Organizer: 第36回日本血栓止血学会学術集会
  • Place of Presentation: 大阪国際交流センター（大阪）
  • Year and Date: 2014-05-29 – 2014-05-31
• [Presentation] 凝固第XIII因子Bサブユニットとフィブリノゲンとの相互作用部位． (2014)
  • Author(s): 惣宇利正善，尾崎 司，一瀬白帝
  • Organizer: 日本生化学会東北支部第80回例会・シンポジウム
  • Place of Presentation: アキタパークホテル（秋田）
  • Year and Date: 2014-05-10
• [Presentation] フィブリン架橋反応における抗XIII因子自己抗体の阻害作用機序． (2013)
  • Author(s): 惣宇利正善，尾崎 司，一瀬白帝
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形国際ホテル（山形）
• [Presentation] The B subunit for coagulation factor XIII accelerates the crosslinking of fibrin in human plasma. (2013)
  • Author(s): Souri M, Osaki T, Ichinose A
  • Organizer: XXIV Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Amsterdam RAI (Amsterdam, Netherlands)