Characterization of the mechanism of biosynthesis for vitamine K dependent proteins and functional study of Vitamin K metabolic enzyme.

• Project/Area Number: 19790224
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Yamagata University
• Principal Investigator: IWATA Hiroki Yamagata University, 医学部, 助教 (70361251)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: プロテインZ / ビタミンK / 生合成 / 発現調節 / ホルモン / 遺伝子多型 / タンパク質化学 / 酵素反応 / 血液凝固因子 / 翻訳後修飾

Research Abstract

We characterized the 5'-flanking region of PZ gene and identified cis-acting sequences and trans-acting factors responsible for the expression of human PZ gene using HepG2. HNF-4α plays a crucial role in PZ gene expression, and that Sp1 acts as an enhancer. The levels of PZ and ZPI in plasma increased during normal pregnancy. It was suggested that the expression of PZ gene was regulated by hormones. And it was confirmed that the expression of PZ gene was enhanced by progesterone.

Research Products

• [Journal Article] ヒトprotein Zの分泌様式 (2010)
  • Author(s): 惣宇利正善, 岩田宏紀, 張偉光, 一瀬白帝
  • Journal Title: 血液・腫瘍科 60(2) Pages: 83-91
  • NAID: 40019064700
  • Peer Reviewed
• [Journal Article] Unique secretion mode of human protein Z: its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion. (2009)
  • Author(s): Souri M, Iwata H, Zhang WG, Ichinose A.
  • Journal Title: Blood 113 Pages: 3857-64
  • Peer Reviewed
• [Journal Article] Unique secretion mode of human protein Z : its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion (2009)
  • Author(s): Souri M
  • Journal Title: Blood 113 Pages: 3857-3864
  • Peer Reviewed
• [Journal Article] Distinct carboxy-terminus of the B subunit, for factor XIII in a population-associated major phenotype : The first case of complete allele-specific alternative splicing products in the coagulation and fibrinolytic systems (2009)
  • Author(s): Iwata H
  • Journal Title: J Thromb Haemost (in press)
  • Peer Reviewed
• [Journal Article] The first two Japanese cases of severe type I congehital plasminogen deficiency with ligneous conjunctivitis : successful treatment with direct thrombin inhibitor and fresh plasma (2009)
  • Author(s): Suzuki T
  • Journal Title: Am J Hemat (in press)
  • Peer Reviewed
• [Journal Article] Unique secretion mode of human protein Z : Its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion (2009)
  • Author(s): Souri M
  • Journal Title: Blood (in press)
  • Peer Reviewed
• [Journal Article] (第42回河口湖心臓討論会)重度プラスミノゲン欠損症における凝固線溶反応の変容 ; 血栓溶解における代替的線溶経路の意義(仮説) (2009)
  • Author(s): 一瀬白帝
  • Journal Title: 心臓 41 Pages: 190-194
• [Journal Article] Regulation of human protein Z gene expression by liver-enriched transcription factor HNF-4alpha and ubiquitous factor Sp1. (2007)
  • Author(s): Sugawara H, Iwata H, Souri M, Ichinose A.
  • Journal Title: J Thromb Haemost. 5 Pages: 2250-8
  • Peer Reviewed
• [Journal Article] Regulation of human protein Z gene expression by liver-enriched transcription factor HNF-4a and ubiquitous factor Sp1. (2007)
  • Author(s): Sugawara, H
  • Journal Title: J Thromb Haemost 5 (11) Pages: 2250-2258
  • Peer Reviewed
• [Presentation] Unique secretion mode of human protein Z:its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion. (2010)
  • Author(s): 惣宇利正善, 張偉光, 岩田宏紀, 一瀬白帝
  • Organizer: 第33回日本血栓止血学会学術集会ISTH 2011 Memorial Award
  • Place of Presentation: 鹿児島
• [Presentation] 翻訳後修飾反応を触媒するγグルタミルカルボキシラーゼは基質タンパク質の細胞内輸送における積荷受容体として働く (2009)
  • Author(s): 惣宇利正善
  • Organizer: 第17回山形分子生物学セミナー
  • Place of Presentation: 鶴岡
  • Year and Date: 2009-12-16
• [Presentation] γ-Glutamyl carboxylase is a cargo receptor for vitamin K-dependent proteins (2009)
  • Author(s): Souri M
  • Organizer: XXII International Society on Thrombosis and Haemostasis(ISTH)Congress with 55th Annual Scientific and Standardization Committee(SSC)Meeting
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2009-07-11
• [Presentation] 正常妊娠と不育症におけるプロテインZおよびプロテインZ依存性プロテアーゼインヒビターの動態 (2009)
  • Author(s): 岩田宏紀
  • Organizer: 第9回TTMフォーラム学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-07
• [Presentation] 妊娠および不育症におけるプロテインZおよびプロテインZ依存性プロテアーゼインヒビターの動態 (2009)
  • Author(s): 岩田宏紀, 杉浦真弓, 一瀬白帝
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州
• [Presentation] 重度Plasminogen欠損症における代替的線溶機構の発動 (2008)
  • Author(s): 岩田宏紀
  • Organizer: 第46回東北止血血栓研究会
  • Place of Presentation: 秋田
  • Year and Date: 2008-09-20
• [Presentation] γ-グルタミルカルボキシラーゼはビタミンK依存性タンパク質のCargo receptorである (2008)
  • Author(s): 惣宇利正善, 岩田宏紀, 張偉光, 中垣智弘, 一瀬白帝
  • Organizer: BMB2008 (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)
  • Place of Presentation: 神戸
• [Presentation] 分泌型ルシフェラーゼを用いたビタミンK依存性タンパク質分泌メカニズムの解析 (2008)
  • Author(s): 惣宇利正善, 岩田宏紀, 張偉光, 中垣智弘, 一瀬白帝
  • Organizer: 第31回日本血栓止血学会学術集会
  • Place of Presentation: 大阪
• [Presentation] γ-グルタミルカルボキシラーゼはビタミンK依存性タンパク質のCargoreceptorである (2008)
  • Author(s): 惣宇利正善
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会学術集会)
  • Place of Presentation: 神戸
• [Presentation] 重度Plasminogen欠損症における代替的線溶機構の解析 (2008)
  • Author(s): 岩田宏紀
  • Organizer: 第31回日本血栓止血学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 本邦初の重度Plasminogen欠損症におけるPlasminogen非依存性代替的線溶機構 (2008)
  • Author(s): 岩田宏紀
  • Organizer: 第6回血液・血管オルビスYoung Investigator Award
  • Place of Presentation: 東京
• [Presentation] 凝固XIII因子Aサブユニットの細胞表面への移動と放出 (2008)
  • Author(s): 惣宇利正善
  • Organizer: 第6回血液・血管オルビス
  • Place of Presentation: 東京
• [Presentation] γ-グルタミルカルボキシラーゼはビタミンK依存性タンパク質の分泌に必須である (2007)
  • Author(s): 惣宇利正善, 岩田宏紀, 張偉光, 一瀬白帝
  • Organizer: 日本生化学会東北支部第73回例会・シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-12
• [Presentation] γ-グルタミルカルボキシラーゼはビタミンK依存性タンパク質の分泌に必須である (2007)
  • Author(s): 惣宇利正善, 岩田宏紀, 張偉光, 一瀬白帝
  • Organizer: 第30回日本血栓止血学会学術集会
  • Place of Presentation: 三重
• [Presentation] Human protein Z gene expression is regulated by HNF-4α and Sp1・independent of warfarin and vitamin K. (2007)
  • Author(s): Sugawara, H
  • Organizer: 21st Congress of the International Society on Thrombosis and Haemostasis (ISTH)
  • Place of Presentation: Switzerland(Geneva)
• [Book] 人工的遺伝子変異導入と発現解析. 図説分子病態学 (2008)
  • Author(s): 岩田宏紀、一瀬白帝
  • Publisher: 中外医学社
• [Book] 図説・分子病態学(改訂4版) (2008)
  • Author(s): 岩田宏紀
  • Publisher: 中外医学社