Mechanism of transcriptional regulation by nuclear receptors

• Project/Area Number: 12219206
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: KATO Shigeaki The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (60204468)
• Co-Investigator(Kenkyū-buntansha): TAKEYAMA Ken-ichi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Assistant Professor, 分子細胞生物学研究所, 助手 (30323570) ; TAKADA Ichiro The University of Tokyo, Institute of Molecular and Cellular Biosciences, Assistant Professor, 分子細胞生物学研究所, 助手 (50361655) ; 北川 浩史 東京大学, 分子細胞生物学研究所, 助手 (20345234)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥125,100,000 (Direct Cost: ¥125,100,000); Fiscal Year 2004: ¥26,000,000 (Direct Cost: ¥26,000,000); Fiscal Year 2003: ¥27,600,000 (Direct Cost: ¥27,600,000); Fiscal Year 2002: ¥25,500,000 (Direct Cost: ¥25,500,000); Fiscal Year 2001: ¥24,000,000 (Direct Cost: ¥24,000,000); Fiscal Year 2000: ¥22,000,000 (Direct Cost: ¥22,000,000)
• Keywords: transcription / co-regulator / sex hormone / nuclear receptor / RNA splicing / 転写制御 / 男性ホルモン受容体異変トランスジェニックマウス / 染色体ヒストンタンパク修飾酵素複合体群 / 細胞周期 / 染色体構造調節因子複合体群 / 性ステロイドホルモン / ホルモン依存性癌 / ホルモン非依存性癌 / 転写共役因子群 / ERα、ERβ / アンドロゲンレセプター(AR) / 性ステロイドホルモン応答性 / SRC-1、TIF2 / TRRAP、GCN5 / リガンド誘導性転写制御因子 / 性ホルモン非依存性生殖器癌発症 / SRC-1、TIF2遺伝子 / 酵母two-hybrid法 / cDNAスクリーニング法 / in vitro転写系 / TRRAP / GCN5転写共役因子複合体 / ステロイドホルモン / 核内ステロイドレセプター / AF-1 / AF-2 / HAT複合体 / 第3の転写共役因子複合体 / 性ホルモン非依存性生殖器癌 / ノックアラトマウス / 核内レセプタークロストーク / 女性ホルモンレセプター(ERα) / MAPキナーゼ / 性ステロイドレセプター種 / 転写共役因子複合体 / クロマチン構造

Research Abstract

The most of prostate and breast cancers are dependent on the actions of sex steroid hormones in tumorigenesis. The actions of sex steroid hormones are believed to be mediated through transcriptional regulations by their nuclear receptors. For hormone-dependent regulations by nuclear receptors, a number of different nuclear complexes have been identified, that include chromatin remodeling and histone modifying complexes. To understand the hormone-induced development of such reproductive organ cancers, we have tried to identify several complexes supporting the sex steroid hormone receptors. One of the receptor-interacting complexes has turned out a spliceosome complex, and this complex physically and functionally associate with the human estrogen receptor a. As this interaction was depending on the phospholiation of the ER by MAP kinase, we propose that cross-talk of estrogen and growth factor signalings in breast cancer development mediates RNA splicing control.

Research Products

• [Journal Article] Splicing potentiation by growth factor signals via estrogen receptor phosphorylation (2005)
  • Author(s): Masuhiro, Y., Mezaki, Y., Takeyama, K., Kato, S., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Splicing potentiation by growth factor signals via estrogen receptor phosphorylation. (2005)
  • Author(s): Masuhiro, Y., Mezaki, Y., Sakari, M., Takeyama, K., Yoshida, T., Inoue, K., Yanagisawa, J., Hanazawa, S., O'Malley, B.W., Kato, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching (2004)
  • Author(s): Murayama, A., Takeyama, K., Kato, S., et al.
  • Journal Title: EMBO J. 23 Pages: 1598-1608
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Brain masculinization requires androgen receptor function (2004)
  • Author(s): Sato, T., Matsumoto, T., Yamada, T., Kato, S., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 1673-1678
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Wnt/β-catenin and estrogen signaling converge in vivo (2004)
  • Author(s): Kouzmenko, A.P., Takeyama, K., Kato, S., et al.
  • Journal Title: J. Biol. Chem. 279 Pages: 40255-40258
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers (2004)
  • Author(s): Maki, A., Zhao, Y., Takeyama, K., Kato, S., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 320 Pages: 262-267
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220 (2004)
  • Author(s): Wada, O., Takada, I., Kato, S., et al.
  • Journal Title: Oncogene 23 Pages: 6000-6005
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. (2004)
  • Author(s): Murayama, A., Kim, M., Yanagisawa, J., Takeyama, K., Kato, S.
  • Journal Title: EMBO J. 23 Pages: 1598-1608
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Brain masculinisation requires androgen receptor function. (2004)
  • Author(s): Sato, T., Matsumoto, T., Kawano, H., Watanabe, T., Uematsu, Y., Sekine, K., Fukuda, T., Aihara, K., Krust, A., Yamada, T., Nakamichi, Y., Yamamoto, Y., Nakamura, T., Yoshimura, K., Yoshizawa, T., Metzger, D., Chambon, P., Kato, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 101 Pages: 1673-1678
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Wnt/β-catenin and estrogen signaling converge in vivo. (2004)
  • Author(s): Kouzmenko, A.P., Takeyama, K., Ito, S., Furutani, T., Sawatsubashi, S., Maki, A., Suzuki, E., Kawasaki, Y., Akiyama, T., Tabata, T., Kato, S.
  • Journal Title: J. Biol. Chem. 279 Pages: 40255-40258
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers. (2004)
  • Author(s): Maki, A., Sawatsubashi, S., Ito, S., Shirode, Y., Suzuki, E., Zhao, Y., Yamagata, K., Kouzmenko, A., Takeyama, K.Kato, S.
  • Journal Title: Biochem. Biophys. Res. Commun. 320 Pages: 262-267
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220 (2004)
  • Author(s): Wada, 0., Oishi, H., Takada, I., Yanagisawa, J., Yano, T., Kato, S.
  • Journal Title: Oncogene 23 Pages: 6000-6005
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Brain masculinization requires androgen receptor function (2004)
  • Author(s): Sato, T., Matsumoto, T., Yamada, T., Kato, S., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 101 Pages: 1673-1678
• [Journal Article] Wnt/β-catenin and estrogen signaling converge in vivo (2004)
  • Author(s): Kouzmenko, A.P., Takeyama, K., Kato, S., et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 40255-40258
• [Journal Article] Juvenile hormones antagonize ecdysone actions through co-repressor recruitment to EcR/USP heterodimers (2004)
  • Author(s): Maki, A., Zhao, Y., Takeyama, K., Kato, S., et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 320 Pages: 262-267
• [Journal Article] In vivo potentiation of human oestrogen receptor α by Cdk7-mediated phosphorylation (2004)
  • Author(s): Ito, S., Takeyama, K., Kato, S., et al.
  • Journal Title: Genes to Cells 9 Pages: 983-992
• [Publications] Sato, T., Matsumoto, T., Kawano, H., Kato, S., et al.: "Brain masculinization requires androgen receptor function"Proc.Natl.Acad.Sci.USA. 101. 1673-1678 (2004)
• [Publications] Murayama, A., Kim, M., Yanagisawa, J., Kato, S., et al.: "Ligand-induced transrepression by a nuclear receptor mediated by a bHLH-type activator through co-regulator switching"EMBO J.. In press. (2004)
• [Publications] Kitagawa, H., Fujiki, R., Yoshimura, K., Kato, S., et al.: "The chromatin remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams Syndrome"Cell. 113. 905-917 (2003)
• [Publications] Ohtake, F., Takeyama, K., Matsumoto, T., Kato, S., et al.: "Modulation of estrogen receptor signalin by association with the activated dioxin receptor"Nature. 423. 545-550 (2003)
• [Publications] Suzawa, M., Takada, I., Yanagisawa, J., Kato, S., et al.: "Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade"Nature Cell Biol.. 5. 224-230 (2003)
• [Publications] Kawano, H., Sato, T., Yamada, T., Kato, S., et al.: "Suppressive function of androgen receptor in bone resorption"Proc.Natl.Acad.Sci.USA. 100. 9416-9421 (2003)
• [Publications] Suzawa, M., Takada, I., Kato S., et al.: "Iinhibition of adipogenesis by cytokines with suppression PPARγ function through the TAK1/TAB1-NIK mediated cascade"Nature Cell Biol.. 5. 224-230 (2003)
• [Publications] Nakamichi, Y., Shukunami, C., Kato S., et al.: "Chondromodulin-I (ChM-I) is a bone remodeling factor"Mol. Cell. Biol.. 23. 636-644 (2003)
• [Publications] Sato, T., Matsumoto, T., Kato S., et al.: "Late onset of obesity in male androgen receptor-deficient (ARKO) mice"Biochem. Biophys. Res. Commun.. 300. 167-171 (2003)
• [Publications] Yanagisawa, J., Kitagawa, H., Kato, S., et al.: "Nuclear receptor function requires a TFTc-type histone acetyl transferase complex"Mol. Cell. 9. 553-562 (2002)
• [Publications] Takeyama, K., Ito, S., et al.: "Androgen-dependent neurodegeneration by potyglutamine-expanded human androgen receptor in drosophila"Neuron. 35. 855-864 (2002)
• [Publications] Kitagawa, H., Yanagisawa, J., Kato S., et al.: "Ligand selective potentiation of rat mineralocorticoid receptor activation function-1 (AF-1) by a CBP-containing HAT complex"Mol. Cell. Biol.. 22. 3698-3706 (2002)
• [Publications] Yanagisawa J., Kitagawa, Kato, S., et al.: "Nuclear receptor function requires a TFTC-type histone acetyl transferase comples"Moll. Cell. (in press). (2002)
• [Publications] Kitagawa, H., Yanagisawa, Kato, S., et al.: "Ligand selective potentiation of rat mineralocorticoid receptor activation function-1 (AF-1 ) by a CBP-containing HAT complex"Mol. Cell. Biol.. (in press). (2002)
• [Publications] Matsui, D., Takeyama, K., Kato, S., et al.: "Transcriptional regulatin of the mouse steroid 5alpha-reductase type II gene by progesterone in brain"Nucleic Acids Research. (in press). (2002)
• [Publications] Van Cromphaut, S.J., Van Herck, E., Kato, S., et al.: "Doudenal calcium absorption in vitmin D receptor-knockout mice : functional and melecular aspects"Proc. Natl. Acad. Sci. USA. 98. 13324-13329 (2001)
• [Publications] Yamamoto, Y., Kato, S., Yanagisawa, J., et al.: "A tamoxifen responsive estrogen receptor alpha mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes"J. Biol. Chem.. 276. 42684-42691 (2001)
• [Publications] Watanabe, M., Yanagisawa, J., Kato, S., et al.: "A subfamily of RNA binding DEAD-box proteins acts as an estrogen receptor α coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA"EMBO J.. 20. 1341-1352 (2001)
• [Publications] Watanabe,M.,Yanagisawa,J.,Kato,S., et al.: "A subfamily of RNA binding DEAD-box proteins acts as an estrogen receptor α co-activator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA."EMBO J.. 20. (2001)
• [Publications] Li,M.,Indra,A.,Kato,S., et al.: "Skin abnormalities generated by temporally-controlled RXRα mutations in adult mouse epidermis."Nature. 407. 633-636 (2000)
• [Publications] Kodera,Y.,Takeyama,K.,Kato,S., et al.: "Ligand-type specific interactions of peroxisome proliferactor-activated receptor gamma with transcriptional coactivators"J.Biol.Chem.. 275. 33201-33204 (2000)
• [Publications] Kobayashi,Y.,Yanagisawa,J.,Kato,S., et al.: "p300 Mediates functional synergism between AF-1 and AF-2 of estrogen receptor α and β by interacting directly with the N-terminal A/B domains."J.Biol., Chem.. 275. 15645-15651 (2000)
• [Publications] Fuse,H.,Kitagawa,H.,Kato.S.: "Characterization of transactivational property and coactivator mediation of rat mineralocorticoid receptor AF-1."Mol.Endocrinol.. 14. 889-899 (2000)
• [Publications] Tai,H.,Kubota,N.,Kato,S.: "In volvement of nuclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells."Biochem.Biophys.Res.Commun.. 267. 311-316 (2000)