Molecular basis of nuclear receptors and their downstream targets in aging

• Project/Area Number: 16109003
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: INOUE Satoshi The University of Tokyo, 医学部・附属病院, 特任教授 (40251251)
• Co-Investigator(Kenkyū-buntansha): URANO Tomohiko 東京大学, 医学部・附属病院, 特任助教 (20334386) ; TSUKUI Toru 埼玉医科大学, 医学部・, 講師 (10333006)
• Project Period (FY): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥115,180,000 (Direct Cost: ¥88,600,000、Indirect Cost: ¥26,580,000); Fiscal Year 2008: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2007: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2006: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2005: ¥27,690,000 (Direct Cost: ¥21,300,000、Indirect Cost: ¥6,390,000); Fiscal Year 2004: ¥32,240,000 (Direct Cost: ¥24,800,000、Indirect Cost: ¥7,440,000)
• Keywords: 老化 / 受容体 / ホルモン / 前立腺がん / ユビキチンリガーゼ / ステロイド / 乳がん / 骨粗鬆症 / 前立腺癌 / 老化病 / エストロゲン / 核内受容体 / トランスジェニック動物 / 老年病 / アデノウイルスベクター / アンドロゲン

Research Abstract

本研究では老化と加齢に伴い増加する疾患における核内受容体とその標的因子、共役因子、修飾因子の新規同定を行い、生理機能ならびに病態における役割を探求した、核内受容体と標的因子の新しい分子作用メカニズム、新規リガンド、シグナル経路を明らかにした。

Research Products

• [Journal Article] Association of estrogen receptor α and histone deacetylase 6 causes rapid decetylation of tubulin in breast cancer cell (2009)
  • Author(s): Azuma K, Urano T, Horie-Inoue K, Hayashi S, Sakai R, Ouchi Y, Inoue S
  • Journal Title: Cancer Res 69 Pages: 2935-2940
  • Peer Reviewed
• [Journal Article] Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth (2009)
  • Author(s): Takayama K, Tsutsumi T, Suzuki T,Horie-Inoue K, Ikeda K, Kaneshiro K, Fujimura T, Kumagai J, Urano T, Sakaki Y, Shirahige K, Sasano H, Takahashi S,Kitamura T, Ouchi Y, Aburatani H, Inoue S
  • Journal Title: Cancer Res 69 Pages: 137-142
  • Peer Reviewed
• [Journal Article] Modulation of adipogenesis-related gene expression by estrogen-related receptor during adipocytic differentiation (2009)
  • Author(s): Kubo M, Ijichi N, Ikeda K, Horie-Inoue K, Takeda S, Inoue S
  • Journal Title: Biochim Biophys Acta -Gene Regulatory Mechanisms 1798 Pages: 71-77
  • Peer Reviewed
• [Journal Article] Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth. (2009)
  • Author(s): Takayama K, Urano T, Inoue S, et al.
  • Journal Title: Cancer Res 69 Pages: 137-142
  • Peer Reviewed
• [Journal Article] EBAG9 is a tumor-promoting and prognostic factor for bladder cancer. (2009)
  • Author(s): Kumagal J, Urano T, Inoue s, et al.
  • Journal Title: Int J Cancer 124 Pages: 799-805
  • Peer Reviewed
• [Journal Article] Modulation of adipogenesis-related gene expression by estrogen-related receptor r during adipocytic differentiation. (2009)
  • Author(s): Kubo M, Ijichi N, Inoue S, et al.
  • Journal Title: Biochim Biophys Acta-Gene Regulatory Mechanlsms 1789 Pages: 71-77
  • Peer Reviewed
• [Journal Article] TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity (2007)
  • Author(s): Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU
  • Journal Title: Nature 446 Pages: 916-921
  • Peer Reviewed
• [Journal Article] Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells (2007)
  • Author(s): Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S
  • Journal Title: J Mol Endocrinol 39 Pages: 239-247
  • Peer Reviewed
• [Journal Article] synuclein stimulates differentiation of osteosarcoma cells : Relevance to downregulation of proteasome activity. (2007)
  • Author(s): Fujita M, Sugama S, Nakai M, Takenouchi T, Wei J, Urano T, Inoue S, Hashimoto M
  • Journal Title: J Biol Chem 282 Pages: 5736-5748
  • Peer Reviewed
• [Journal Article] TRIM25RING-finger E3 ubiquitin ligase is essential fbr RIG-I-mediatedantiviral activity (2007)
  • Author(s): Gack MU, Inoue S, Jung JU, et. al.
  • Journal Title: Naature 446 Pages: 916-921
  • Peer Reviewed
• [Journal Article] Increased expression of Estrogen-Related Receptor alpha(ERRalpha) is aneative proostic predictor in human prostate cancer (2007)
  • Author(s): Fujimura T, Urano T, Inoue S, et. al.
  • Journal Title: Int J Cancer 120 Pages: 2325-2330
  • Peer Reviewed
• [Journal Article] Nuclear cyclin Bl in human breast carcinoma as a potent prognostic factor (2007)
  • Author(s): Suzuki T, Inoue S, Sasano H, et. al.
  • Journal Title: Cancer Sci 98 Pages: 644-651
  • Peer Reviewed
• [Journal Article] Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer (2007)
  • Author(s): Kumagai J, Urano T, Ihoue S, et. al.
  • Journal Title: Prostate 67 Pages: 1029-1037
  • Peer Reviewed
• [Journal Article] Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adioce differentiation (2007)
  • Author(s): Ijichi N, Ikeda K, Ihoue S, et. al.
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 813-818
  • Peer Reviewed
• [Journal Article] Vitamin K2 induces phosphorylation of protein kinase A and expression of novel taret genes in osteoblastic cells (2007)
  • Author(s): Ichikawa T, Horie-Inoue K, Inoue S, et. al.
  • Journal Title: JMol Endocrinol 39 Pages: 239-247
  • Peer Reviewed
• [Journal Article] Alpha-synuclein stimulates differentiation of osteosarcoma cells : Relevance to downregulation of proteasome activity. (2007)
  • Author(s): Fujita M et al.
  • Journal Title: J Biol Chem 282 Pages: 5736-5748
• [Journal Article] TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. (2007)
  • Author(s): Gack MU et al.
  • Journal Title: Nature 446 Pages: 916-921
• [Journal Article] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells (2006)
  • Author(s): Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S
  • Journal Title: J Biol Chem 281 Pages: 16927-16934
  • Peer Reviewed
• [Journal Article] 17ss-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxindependent redox regulation of Akt in myocardiac H9c2 cell (2006)
  • Author(s): Urata Y, Ihara Y, Murata H, Goto S, Koji T, Yodoi J, Inoue S, Kondo T
  • Journal Title: J Biol Chem 281 Pages: 13092-13102
  • Peer Reviewed
• [Journal Article] 17-beta-Estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cell. (2006)
  • Author(s): Urata Y et al.
  • Journal Title: J Biol Chem 281 Pages: 13092-13102
• [Journal Article] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006)
  • Author(s): Ichikawa T et al.
  • Journal Title: J Biol Chem 281 Pages: 16927-16934
• [Journal Article] Identification of novel steroid target genes through the combination of bioinformatics and functional analysis of hormone response elements. (2006)
  • Author(s): Horie-Inoue K, Takayama K, Inoue S et al.
  • Journal Title: Biochem Biophys Res Commun 339 Pages: 99-106
• [Journal Article] Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma (2005)
  • Author(s): Ogushi T, Takahashi S, Takeuchi T, Urano T, Horie-Inoue K, Kumagai J, Kitamura T, Ouchi Y, Muramatsu M, Inoue S
  • Journal Title: Cancer Res 65 Pages: 3700-3706
  • Peer Reviewed
• [Journal Article] Estrogen-responsive finger protein as a new potential biomarker for breast cancer (2005)
  • Author(s): Suzuki T, Urano T, Tsukui T, Horie-Inoue K,Moriya T, Ishida T, Muramatasu M, Ouchi Y,Sasano H, Inoue S
  • Journal Title: Clin Cancer Res 11 Pages: 6148-6154
• [Journal Article] 14-3-3 in endometrial cancer A possible prognostic marker in early stage cancer (2005)
  • Author(s): Ito K, Suzuki T, Akahira J, Sakuma M,Saitou S, Okamoto S, Niikura H, Okamura K,Yaegashi N, Sasano H, Inoue S
  • Journal Title: Clin Caner Res 11 Pages: 7384-7391
  • Peer Reviewed
• [Journal Article] Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma. (2005)
  • Author(s): Ogushi T, Takahashi S, Inoue S et al.
  • Journal Title: Cancer Res 65 Pages: 3700-3706
• [Journal Article] Survival versus apoptotic 17beta-estradiol effect : Role of ER alpha and ER beta activated non-genomic signaling. (2005)
  • Author(s): Acconcia F, Inoue S, Mario M et al.
  • Journal Title: J Cell Physiol 203 Pages: 193-201
• [Journal Article] 14-3-3 sigma in endometrial cancer - A possible prognostic marker in early stage cancer -. (2005)
  • Author(s): Ito K, Suzuki T, Inoue S et al.
  • Journal Title: Clin Caner Res 11 Pages: 7384-7391
• [Journal Article] Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma. (2005)
  • Author(s): Azuma K, Inoue S, Sakai R et al.
  • Journal Title: Oncogene 24 Pages: 4754-4764
• [Journal Article] Estrogen-responsive finger protein as a new potential biomarker for breast cancer. (2005)
  • Author(s): Suzuki T, Urano T, Inoue S et al.
  • Journal Title: Clin Cancer Res 11 Pages: 6148-6154
• [Journal Article] Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription (2004)
  • Author(s): Ikeda K, Ogawa S, Tsukui T, Horie-Inoue K,Ouchi Y, Kato S, Muramatsu M, Inoue S
  • Journal Title: Mol Endocrinol 18 Pages: 1131-1143
  • Peer Reviewed
• [Journal Article] Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription. (2004)
  • Author(s): Ikeda K, Muramatsu M, Inoue S et al.
  • Journal Title: Mol Endocrinol 18 Pages: 1131-1143
• [Journal Article] Analysis or estrogen receptor alpha signaling complex at the plasma membrane. (2004)
  • Author(s): Azuma K, Inoue S, Sakai R et al.
  • Journal Title: FEBS Lett 577 Pages: 1296-1301
• [Journal Article] Molecular mechanism of estrogen action and its role in bone metabolism and brain functions. (2004)
  • Author(s): Inoue S
  • Journal Title: Internal Med 43 Pages: 150-151
• [Journal Article] Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues. (2004)
  • Author(s): Shimada N, Inoue S, Sasano H et al.
  • Journal Title: Mol Cell Endocrinol 218 Pages: 147-153
• [Journal Article] Identification and functional analysis of consensus androgen response elements in human prostate cancer cells. (2004)
  • Author(s): Horie-Inoue K, Bono H, Inoue S et al.
  • Journal Title: Biochem Biophys Res Commun 325 Pages: 1312-1317
• [Journal Article] Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I.
  • Author(s): Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, Garcia-Sastre A
  • Journal Title: Cell Host , Microbe (in press)
  • Peer Reviewed
• [Journal Article] The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
  • Author(s): Suzuki H, Inoue S, Hayashizaki Y(他157名)
  • Journal Title: Nat Genet (in press)
  • Peer Reviewed
• [Journal Article] Identification of Igf2, Igfbp2 and Enpp2 as estrogen-responsive genes in rat hippocampus
  • Author(s): Takeo C, Ikeda K, Horie-Inoue K, Inoue S
  • Journal Title: Endocrine J (in press)
  • Peer Reviewed
• [Journal Article] Identification of Igf2, Igfbp2 and Enpp2 as Estrogen-Responsive Genes in Rat Hippocampus.
  • Author(s): Takeo C, Ikeda K, Inoue S, et al.
  • Journal Title: Endocrine J (In press)
  • Peer Reviewed
• [Journal Article] Association of estrofen receptor a and histone deacetylase 6 causes rapid decetylation of tubulin in breast cancer cell.
  • Author(s): Azuma K, Urano T, Inoue S, et al.
  • Journal Title: Cancer Res (in press)
  • Peer Reviewed
• [Journal Article] Increased expression of Estrogen-Related Receptor alpha (ERRalpha) is a negative prognostic predictor in human prostate cancer.
  • Author(s): Fujimura T et al.
  • Journal Title: Int J Cancer (in press)
• [Journal Article] Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic micro array analysis.
  • Author(s): Takayama K et al.
  • Journal Title: Oncogene (in press)
• [Journal Article] Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carsinoma.
  • Author(s): Ogushi T, Takahashi S, Inoue S et al.
  • Journal Title: Cancer Res (in press)
• [Presentation] [シンポジウム]エストロゲンレセプターとエネルギー代謝 (2008)
  • Author(s): 井上聡
  • 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
  • Year and Date: 2008-12-09
• [Presentation] [Symposium, Invited Talk] Newestrogen target genes (2008)
  • Author(s): Inoue S
  • Organizer: 13^<th> International Congress of Endocrinology, Rio de Janeiro
  • Place of Presentation: Brazil
• [Presentation] [Invited Talk]New Target Genes forSteroid Hormones (2008)
  • Author(s): Inoue S
  • Organizer: CBI Annual Meeting 2008 International Symposium
  • Place of Presentation: Tokyo, Japan
• [Presentation] [特別講演]女性ホルモンの作用機構とホルモン補充療法 (2008)
  • Author(s): 井上聡
  • Organizer: 第26回日本美容皮膚科学会総会
  • Place of Presentation: 大阪
• [Presentation] [Invited Talk]Protein modification of 14-3-3sigma by TRIM E3 ligase (2008)
  • Author(s): Inoue S
  • Organizer: Biology of 14-3-3 Proteins
  • Place of Presentation: Gordon Research Conferences, Ventura,California, USA
• [Presentation] [Symposium]Prevention and Treatment of Osteoporosis (2008)
  • Author(s): Inoue S
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] [Invited Talk]Protein modification of 14-3-3sigma by TRIME3 ligase. (2008)
  • Author(s): Inoue S
  • Organizer: Biology of 14-3-3 Proteins, Gordon Research Conferences
  • Place of Presentation: Ventura,California,USA
• [Presentation] [Invited Talk] Novel Vitamin K action via transcriptional regulation (2007)
  • Author(s): Inoue S
  • Organizer: 4^<th> Meeting of Bone Biology Forum
  • Place of Presentation: Shizuoka, Japan
  • Year and Date: 2007-08-24
• [Presentation] [シンポジウム]核内レセプターと糖脂質代謝の最前線:エストロゲン・エストロゲン関連レセプターER/ERRとエネルギー代謝 (2007)
  • Author(s): 井上 聡
  • Organizer: 第80回日本内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] Estrogen responsive genes in the growth control of breast tumors. (2007)
  • Author(s): Inoue S
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 骨におけるビタミンKの作用メカニズムーGammaカルボキシル化による蛋白修飾と核内受容体を介する転写制御 (2007)
  • Author(s): 井上 聡
  • Organizer: 第9回日本骨粗髪症学会
  • Place of Presentation: 東京
• [Presentation] [Workshop]脂溶性ビタミンの分子生物学:ビタミンKの骨における新しい作用メカニズム (2007)
  • Author(s): 井上 聡
  • Organizer: BMB2007(第80回日本生化学会大会・第30回日本分子生物学会年会)
  • Place of Presentation: 横浜
• [Presentation] [研究奨励賞受賞講演]エストロゲン標的遺伝子の同定とその機能の解明 (2006)
  • Author(s): 井上聡
  • Organizer: 第79回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2006-05-19
• [Presentation] [Invited Talk] Post-translational modification of 14-3-3sigma by E3 ligase Efp (2006)
  • Author(s): Inoue S
  • Organizer: 2006 GRC on Biology of 14-3-3 Protein
  • Place of Presentation: Gordon Research Conference, Oxford, UK
• [Presentation] [学術賞受賞講演] 骨代謝疾患の治療薬作用機構ならびに疾患遺伝子の探索 (2006)
  • Author(s): 井上聡
  • Organizer: 第24回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] [Luncheon Seminar] Novel mechanism of vitamin K action via transcriptional regulation (2005)
  • Author(s): Inoue S
  • Organizer: International Interdisciplinary Conference on Vitamins, Coenzymes, and Biofactors 2005
  • Place of Presentation: Awaji, Japan
• [Presentation] [Symposium]"Molecular and cellular analysis of steroid hormone receptor : Expression and its role in reproductive organs"Estrogen receptors and their downstream targets in b east tumors (2004)
  • Author(s): Inoue S
  • Organizer: 16^<th> International Congress of the IFAA (International Federation of Associations of Anatomists
  • Place of Presentation: Kyoto, Japan
• [Book] 40歳からの女性の医学骨粗鬆症-骨のアンチエイジング- (2008)
  • Author(s): 井上聡
  • Total Pages: 111
  • Publisher: 岩波書店
• [Book] 【内分泌系】核内受容体とアンチエイジング:水島裕監修:アンチエイジング・ヘルスフード (2008)
  • Author(s): 井上 聡
  • Total Pages: 464
  • Publisher: サイエンスフォーラム
• [Book] Handbook of Immunohistochemistry and in situ hybridization of human carcinomas Volume 3. Molecular genetics, liver carcinoma, and pancreatic carcinoma (2005)
  • Author(s): Aoki T, Imamura H, Makuuchi M, Inoue S
  • Total Pages: 480
  • Publisher: Elsevier Academic Press
• [Book] Zinc finger proteins : from atomic contact to cellular function (2004)
  • Author(s): Ikeda K, Inoue S, Muramatsu M
  • Total Pages: 290
  • Publisher: Landes Bioscience
• [Remarks]
  • URL: http://www.h.u-tokyo.ac.jp/center22/koukarei.html