Expression of nuclear receptor CAR during G1 in human cells and its role in cell proliferation

• Project/Area Number: 19590070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: SUGATANI Junko University of Shizuoka, 薬学部, 教授 (30098131)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 核内受容体 / CAR / 転写調節 / 細胞周期 / 血清飢餓ストレス / Elk / チェックポイント

Research Abstract

核内受容体CARは、CYP2B、UGT1A1等の薬物代謝酵素/トランスポーター遺伝子転写に中心的役割を演じている細胞内因子である。本研究では細胞周期に依存したCARの発現調節機構とその新規な役割について解析し、細胞周期を調節するCDK4シグナルによってCARの発現が制御されG1期早期に発現すること、血清飢餓ストレスによるElkを介した新規な応答機構の存在を明らかにすることができ、CARが薬物代謝酵素だけでなく細胞増殖関連因子の転写調節にも深く関わっている可能性が示された。

Research Products

• [Journal Article] Up-regulation of CAR expression through Elk-1 in HepG2 and SW480 cells by serum starvation stress (2009)
  • Author(s): M. Osabe, J. Sugatani, A. Takemura, M. Kurosawa, Y. Yamazaki, A. Ikari, M. Miwa
  • Journal Title: FEBS Letters 583(5)[IF 3.263] Pages: 885-889
• [Journal Article] Up-regulation of CAR expression through E1k-1 in HepG2 and SW480 cells by serum starvation stress (2009)
  • Author(s): M. Osabe, J. Sugatani, A. Takemura, M. Kurosawa, Y. Yamazaki, A. Ikari, M. Miwa
  • Journal Title: FEBS Letters 583(5) Pages: 885-889
  • Peer Reviewed
• [Journal Article] Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation (2008)
  • Author(s): M. Osabe, J. Sugatani, A. Takemura, Y. Yamazaki, A. Ikari, N. Kitamura, M. Negishi, M. Miwa
  • Journal Title: Biochem. Biophys. Res. Commun 369(4)[IF 2.855] Pages: 1027-1033
• [Journal Article] Surface localization of the nuclear receptor CAR in influenza A virus-infected cells (2008)
  • Author(s): T. Takahashi, Y. Moriyama, A. Ikari, J. Sugatani T. Suzuki, M. Miwa
  • Journal Title: Biochem. Biophys. Res. Commun 368(3)[IF 2.855] Pages: 550-555
• [Journal Article] PPP1R16A, the membrane subunit of protein phosphatase1b, signals nuclear translocation of the nuclear receptor CAR (2008)
  • Author(s): T. Sueyoshi, R. Moore, J. Sugatani Y. Matsumura, M. Negishi
  • Journal Title: Mol. Pharmacol 73(4)[IF 4.469] Pages: 1113-1121
• [Journal Article] Constitutive androstane receptor and peroxisome proliferator-activated receptor a are activated in liver of male rats fed a high-fat and high-sucrose diet and the hepatic expression of UGT1A1 and UGT1A6 is enhanced (2008)
  • Author(s): M. Osabe, J. Sugatani, T. Fukuyama, S. Ikushiro, A. Ikari, M. Miwa
  • Journal Title: Drug Metab. Dispos 36(2)[IF 3.638] Pages: 294-302
• [Journal Article] Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs : implication of defects in the UGT1A1 gene promoter (2008)
  • Author(s): J. Sugatani, K. Mizushima, M. Osabe, K. Yamakawa, S. Kakizaki, H. Takagi, M. Mori, A. Ikari, M. Miwa
  • Journal Title: Naunyn Schmiedebergs Arch. Pharmacol 377(4-6)[IF 2.779] Pages: 597-605
• [Journal Article] Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation. (2008)
  • Author(s): M. Osabe, J. Sugatani, A. Takemura, Y. Yamazaki, A. Ikari, N. Kitamura, M. Negishi, M. Miwa
  • Journal Title: Biochem. Biophys. Res. Commun. 369(4) Pages: 1027-1033
  • Peer Reviewed
• [Journal Article] PPP1R16A, the membrane subunit of protein phosphatase 1b, signals nuclear translocation of the nuclear receptor CAR. (2008)
  • Author(s): T. Sueyoshi, R. Moore, J. Sugatani, Y. Matsumura, M. Negishi
  • Journal Title: Mol. Pharmacol. 73(4) Pages: 1113-1121
  • Peer Reviewed
• [Journal Article] Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation. (2008)
  • Author(s): Osabe M., et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 369(4) Pages: 1027-1033
  • Peer Reviewed
• [Journal Article] PPP1RI6A, the membrane subunit of protein phosphatase 1b, signals nuclear translocation of the nuclear receptor CAR. (2008)
  • Author(s): Sueyoshi T., et. al.
  • Journal Title: Mol. Pharmacol. 73(4) Pages: 1113-1121
  • Peer Reviewed
• [Presentation] 血清飢餓ストレスによる核内受容体CARの発現誘導機構 (2009)
  • Author(s): 竹村明子、黒澤雅俊、長部誠、山崎泰広、五十里彰、菅谷純子
  • Organizer: 日本薬学会第129年会(講演要旨集3)
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] サイクリン依存性キナーゼ2はヒトUDP-グルクロン酸転移酵素UGT1A1発現を抑制する (2009)
  • Author(s): 黒澤雅俊、竹村明子、長部誠、山崎泰広、五十里彰、菅谷純子
  • Organizer: 日本薬学会第129年会(講演要旨集3)
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] 血清飢餓ストレスによる核内受容体CARの発現誘導機構 (2009)
  • Author(s): 竹村明子, 黒澤雅俊, 長部誠, 山崎康広, 五十里彰, 菅谷純子
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] ストレス刺激により誘導される核内受容体CARの発現調節機構の解析BMB2008 (2008)
  • Author(s): 菅谷純子、長部誠、竹村明子、黒澤雅俊、山崎泰広、五十里彰、三輪匡男
  • Organizer: 第81回日本生化学会大会(講演要旨集)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ストレス刺激により誘導される核内受容体CARの発現調節機構の解析 (2008)
  • Author(s): 菅谷純子, 長部 誠, 竹村明子, 黒澤雅俊, 山崎泰広, 五十里彰, 三輪匡男
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 細胞生育環境によるUGT1A1発現変動の解析 (2008)
  • Author(s): 菅谷純子、長部誠、竹村明子、黒澤雅俊、山崎泰広、五十里彰、三輪匡男
  • Organizer: 第11回P450研究会、第3回UGT研究会合同開催
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-25
• [Presentation] 細胞周期に依存した薬物代謝酵素誘導の解析 (2008)
  • Author(s): 竹村明子、長部誠、黒澤雅俊、山崎泰広、五十里彰、菅谷純子
  • Organizer: 第54回日本薬学会東海支部総会・大会(講演要旨集)
  • Place of Presentation: 名古屋
  • Year and Date: 2008-07-05
• [Presentation] 核内受容体CARの細胞周期に基づく発現制御とその機能について (2008)
  • Author(s): 長部誠、菅谷純子、福山知哲、竹村明子、山崎泰広、五十里彰、三輪匡男
  • Organizer: 日本薬学会第128年会(講演要旨集3)
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Presentation] 核内受容体CARの細胞周期に基づく発現制御とその機能について (2008)
  • Author(s): 長部誠、菅谷純子、福山知哲、竹村明子、山崎康広、五十里彰、三輪匡男
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Presentation] Transcriptional regulation of UGT1A1 gene expression and its cell-cycle-dependent ecpression by nuclear receptor CAR (2008)
  • Author(s): Junko Sugatani, Makoto Osabe, Akiko Takemura, Yasuhiro Yamazaki, Akira Ikari, Masao Miwa
  • Organizer: The 12th International Glucuronidation and UGT Workshop
  • Place of Presentation: Quebec, Canada
• [Presentation] Expression of CAR and its function associated with cell cycle. BMB2007 (2007)
  • Author(s): Makoto Osabe, Junko Sugatani, Tomoaki Fukuyama, Yasuhiro Yamazaki, Akira Ikari, Masao Miwa
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Expression of CAR and its function associated with cell cycle (2007)
  • Author(s): Makoto Osabe, Junko Sugatani, Tomoaki Fukuyama, Yasuhiro Yamazaki, Akira Ikari, Masao Miwa
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 細胞生育環境に依存した核内受容体CAR発現調節 (2007)
  • Author(s): 長部誠、菅谷純子、福山知哲、水嶋康介、高橋忠伸、五十里彰、三輪匡男
  • Organizer: 第127年回日本薬学会(講演要旨集)
  • Place of Presentation: 富山
  • Year and Date: 2007-03-30
• [Presentation] Transcriptional regulation of human UGT1A1 gene expression through distal and proximal reporter genes by nuclear receptors (2007)
  • Author(s): Junko Sugatani, Kousuke Mizushima, Makoto Osabe, Tadanobu Takahashi, Akira Ikari, Masao Miwa
  • Organizer: The 5th International Symposium on Receptor Mechanisms, Signal Transduction and Drug Effects, International Receptor Symposium
  • Place of Presentation: Shizuoka, Japan
• [Book] 加水分解酵素3.1.4.39-3.1.4.51、4.6.1.14「酵素ハンドブック(第3版)」(八木達彦、福井俊郎、一島英治、鏡山博行、虎谷哲夫編集) (2008)
  • Author(s): 菅谷純子,三輪匡男
  • Publisher: 朝倉書店
• [Book] 酵素ハンドブック(第3版) (2008)
  • Author(s): 菅谷純子, 三輪匡男
  • Publisher: 朝倉書店