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脂質合成系調節転写因子SREBP-1/2の標的配列特異性を決定する共因子の解明

Research Project

Project/Area Number 20052006
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Tsukuba

Principal Investigator

島野 仁  University of Tsukuba, 大学院・人間総合科学研究科, 教授 (20251241)

Co-Investigator(Kenkyū-buntansha) 矢作 直也  東京大学, 大学院・医学系研究科, 特任准教授 (60420246)
中川 嘉  筑波大学, 大学院・人間総合科学研究科, 講師 (80361351)
松坂 賢  筑波大学, 大学院・人間総合科学研究科, 助教 (70400679)
山田 信博  筑波大学, 大学院・人間総合科学研究科, 教授 (40200729)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2009: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2008: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywords中性脂肪 / コレステロール / 転写調節 / エネルギー代謝 / メタボリックシンドローム
Research Abstract

一定の機能をもった遺伝子群の発現制御機構の解明はポストゲノム時代の中心課題である。我々は、生活習慣病のsusceptibilityを規定する遺伝子の候補として、Sterol regulatory element-binding protein-1(SREBP-1)という転写因子に以前から着目して解析してきた。SREBP-1は、脂肪酸、トリグリセリド合成系の諸酵素の発現調節に最も重要な働きをしていると考えられている転写因子であり、炭水化物を脂肪へ変換して体内のエネルギー貯蔵を高める方向へと作用する倹約遺伝子のひとつとして注目されている。SREBP-1の標的遺伝子の発現調節機構の解明やその調節領域の多型性の解析はエネルギー代謝ホメオスタシスの生理機構、生活習慣病の病態いずれの理解にも重要である。SREBP-1が標的配列SREと結合し転写活性を発揮する際、他の共因子やDNA配列とどのように相互作用して転写効率が制御されていくのかそのメカニズムを探求していくことが我々のテーマであるエネルギー代謝制御の解明の第一歩と考えている。そのためには複数の転写因子間の相互作用やコファクターについて知見を深めていくことが必要である。またそれらの複合体形成因子は細胞・臓器特異的な存在様式をとっている可能性が高く、そういう観点からin vivoの臓器で検討を重ねる必要もある。本年度の研究実績として、in vivoの臓器での解析からSREBP-1cの遺伝子発現制御に重要なLiver X Receptorと相互作用する新たなタンパクを同定し、また、その分子がSREBP-1cを介してトリグリセリド合成系の調節にどのように関与するかを明らかにした。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2010 2009 2008 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (6 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription2010

    • Author(s)
      Furumatsu T, Shukunami C, Amemiya-Kudo M, Shimano H, Ozaki T.
    • Journal Title

      Int J Biochem Cell Biol 42

      Pages: 148-156

    • NAID

      120003338814

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPARalpha2010

    • Author(s)
      Danno H, Ishii KA, Nakagawa Y, Mikami M, Yamamoto T, Yabe S, Furusawa M, Kumadaki S, Watanabe K, Shimizu H, Matsuzaka T, Kobayashi K, Takahashi A, Yatoh S, Suzuki H, Yamada N, Shimano H
    • Journal Title

      Biochem Biophys Res Commun 391

      Pages: 1222-1227

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit2010

    • Author(s)
      Takeuchi Y, Yahagi N, Izumida Y, Nishi M, Kubota M, Teraoka Y, Yamamoto T, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Ohashi K, Osuga JI, Gotoda T, Ishibashi S, Itaka K, Kataoka K, Nagai R, Yamada N, Kadowaki T, Shimano H.
    • Journal Title

      J Biol Chem 285

      Pages: 11681-11691

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SCAP is required for timely and proper myelin membrane synthesis2009

    • Author(s)
      Verheijen MH, Camargo N, Verdier V, Nadra K, de Preux Charles AS, Medard JJ, Luoma A, Crowther M, Inouye H, Shimano H, Chen S, Brouwers JF, Helms JB, Feltri ML, Wrabetz L, Kirschner D, Chrast R, Smit AB
    • Journal Title

      Proc Natl Acad Sci USA 106

      Pages: 21383-21388

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of pitavastatin(LIVALO Tablet)on high density lipoprotein cholesterol(HDL-C)in hypercholesterolemia2009

    • Author(s)
      Teramoto T, Shimano H, Yokote K, Urashima M
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 654-661

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin and adiponectin receptors in human pheochromocytoma2009

    • Author(s)
      Isobe K, Fu L, Tatsuno I, Takahashi H, Nissato S, Hara H, Yashiro T, Suzukawa K, Takekoshi K, Shimano H, Kawakami Y
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 442-447

    • NAID

      10025766556

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN2009

    • Author(s)
      Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, Gunn A, Nakagawa Y, Shimano H, Todorov I, Rossi JJ, Natarajan R
    • Journal Title

      Nat Cell Biol 11

      Pages: 881-889

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice2009

    • Author(s)
      Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H
    • Journal Title

      Biochem Biophys Res Commun 385

      Pages: 492-496

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women : a meta-analysis2009

    • Author(s)
      Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M, Sugawara A, Totsuka K, Shimano H, Ohashi Y, Yamada N, Sone H
    • Journal Title

      JAMA 301

      Pages: 2024-2035

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes : a meta-analysis2009

    • Author(s)
      Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Sato M, Sugawara A, Totsuka K, Shimano H, Ohashi Y, Yamada N, Sone H
    • Journal Title

      Diabetes Care 32

      Pages: 959-965

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elov16 : a new player in fatty acid metabolism and insulin sensitivity2009

    • Author(s)
      Matsuzaka T, Shimano H
    • Journal Title

      J Mol Med 87

      Pages: 379-384

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SREBPs : Febnovel aspects of SREBPs in the regulation of lipid synthesis2009

    • Author(s)
      Shimano H
    • Journal Title

      FEBS J 276

      Pages: 615-615

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SREBPs : physiology and pathophysiology of the SREBP family2009

    • Author(s)
      Shimano H
    • Journal Title

      FEBS J 276

      Pages: 616-621

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SPARC is a major secretory gene expressed and involved in the development of proliferative diabetic retinopathy2009

    • Author(s)
      Watanabe K, Okamoto F, Yokoo T, Tada Iida K, Suzuki H, Shimano H, Oshika T, Yamada N, Toyoshima H
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 69-76

    • NAID

      10025764920

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep(ob)(/)(ob)mice2009

    • Author(s)
      Sekiya M, Yahagi N, Tamura Y, Okazaki H, Igarashi M, Ohta K, Takanashi M, Kumagai M, Takase S, Nishi M, Takeuchi Y, Izumida Y, Kubota M, Ohashi K, Iizuka Y, Yagyu H, Gotoda T, Nagai R, Shimano H, Yamada N, Kadowaki T, Ishibashi S, Osuga JI.
    • Journal Title

      Biochem Biophys Res Commun 387

      Pages: 511-515

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of neutral cholesterol ester hydrolase 1 accelerates atherosclerosis2009

    • Author(s)
      Sekiya M, Osuga J, Nagashima S, Ohshiro T, Igarashi M, Okazaki H, Takahashi M, Tazoe F, Wada T, Ohta K, Takanashi M, Kumagai M, Nishi M, Takase S, Yahagi N, Yagyu H, Ohashi K, Nagai R, Kadowaki T, Furukawa Y, Ishibashi S.
    • Journal Title

      Cell Metab 10

      Pages: 219-228

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of nuclear SREBP-2 in pancreatic beta -cells results in cholesterol accumulation leading to insulin secretion defects and diabetea : A new model for beta -cell linotoxicity2008

    • Author(s)
      Ishikawa M, et.al.
    • Journal Title

      J Lipid Res 49

      Pages: 2524-2534

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hormone-sensitive lipase is involved in hepatic, cholesterol ester hydrolysis.2008

    • Author(s)
      Sekiya M, et.al.
    • Journal Title

      J Lipid Res 49

      Pages: 1829-1838

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-lc in pancreatic islets.2008

    • Author(s)
      Kato T, et.al.
    • Journal Title

      Diabetes 57

      Pages: 2382-2392

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin-dependent kinase inhibitor, p21WA.F1/CIP1, is involved in adipocyto differentiation and hypertrophy, linking to obesity and insulin resistance.2008

    • Author(s)
      Inoue N, et.al.
    • Journal Title

      J Biol Chem 282

      Pages: 21220-21229

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mouse Elov1-6 promoter is an SREBP. Target2008

    • Author(s)
      Kumadaki S, et.al.
    • Journal Title

      Biochem Biophys Res Commun 368

      Pages: 261-266

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] エネルギー代謝転写因子ネットワーク破綻による動脈硬化リスク形成の病態 Disturb ances in energy transcription factor network and formation of risks for atherosclerosis2009

    • Author(s)
      島野仁
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      下関
    • Related Report
      2009 Annual Research Report
  • [Presentation] Proposed Guidelines for Hypertriglyceridemia in Japan with Non-HDL Cholesterol as the Secondary Target2009

    • Author(s)
      島野仁
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      下関
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cyclin-Dependent Kinase Inhibitor, p21WAF1/CIP1, is Involved in Adipocyte Differentiation and Hypertrophy, Linking to Obesity, and Insulin Resistance2009

    • Author(s)
      矢作直也
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      下関
    • Related Report
      2009 Annual Research Report
  • [Presentation] in vivoにおけるEPAによるsREBP-1c転写活性抑制メカニズムの解析2008

    • Author(s)
      武内謙憲、他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] 転写制御を介したエネルギー代謝調節と動脈硬化2008

    • Author(s)
      矢作直也、他
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      筑波
    • Related Report
      2008 Annual Research Report
  • [Presentation] in vivoにおけるEPAによるSREBP-1c転写活性抑制メカニズムの解析2008

    • Author(s)
      武内謙憲、他
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      筑波
    • Related Report
      2008 Annual Research Report
  • [Book] 脂肪酸の相違によるインスリン抵抗性への影響 Annual Review 糖尿病・代謝、内分泌20092009

    • Author(s)
      島野仁
    • Total Pages
      150
    • Publisher
      中外医学社
    • Related Report
      2009 Annual Research Report
  • [Book] 糖尿病薬(インスリン抵抗性改善薬)、治療薬イラストレイテッド改訂版2009

    • Author(s)
      島野仁
    • Total Pages
      124
    • Publisher
      羊土社
    • Related Report
      2009 Annual Research Report
  • [Book] 文系MRのための糖尿病自己学習ノート2009

    • Author(s)
      矢作直也、大西由希子
    • Total Pages
      124
    • Publisher
      株式会社SCICUS
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/endocrinology/research/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/clinical-med/endocrinology/research/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-04-17  

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