Cloning of androgen receptor AF-1 specific cbactivator gene and development of new drug

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 13357010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Endocrinology
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: NAWATA Hajime Kyushu University, Department of medicine, professor, 大学院・医学研究院, 教授 (10038820)
• Co-Investigator(Kenkyū-buntansha): YANASE Toshihiko Kyushu University, associate professor, 大学院・医学研究院, 助教授 (30239818) ; GOTO Kiminobu Kyushu University, assistant professor, 大学病院, 助手 (90284512) ; OKABE Taijiroh Kyushu University, assistant professor, 大学病院, 助手 (40264030) ; NOMURA Masahiro Kyushu University, assistant professor, 大学病院, 助手 (30315080)
• Project Period (FY): 2001 – 2003
• Keywords: androgen receptor / ANT-1 / splicing factor compartment / TPR structure / functional domein

Research Abstract

In the androgen receptor (AR), most of its transactivation activity is mediated via the activation function -1(AF-1). By employing yeast two-hybrid assay, we isolated a cDNA sequence encoding a protein binding to AR-AF-1. This protein, named ANT-1(AR N-terminal domain transactivating protein-1), enhanced the ligand-independent autonomous AF-1 transactivation function of AR or glucocorticoid receptor, but did not enhance that of estrogen receptor α. In contrast, the ANT-1 did not enhance any ligand-dependent AF-2 activities. Furthermore, the ligand-independent interaction between AR-AF-1 and ANT-1 was confirmed in vivo and in vitro. The ANT-1 sequence was identical to that of a protein that binds to U5 small nuclear ribonucleoprotein particle, a human homologue of yeast splicing factor Prp6p, involved in spliceosome. ANT-1 was compartmentalized into 20-40 coarse splicing factor compartment speckles against the background of the diffuse reticular distribution. AR colocalized with ANT-1 only in the diffusely distributed area, whereas the ANT-1 speckles were spatially distinct from but surrounded by the AR compartments. The active gene transcription has been shown to periphery of the splicing factor compartment. The molecular interaction between two spatially distinct subnuclear compartments mediated by ANT-1 may therefore recruit AR into the transcription-splicing-coupling machinery.

Research Products

• [Journal Article] Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. (2003)
  • Author(s): Lu, ZH., Mu, YM., Wang, BA., Li, XL., Lu, JM., Li, JY,.Pan, CY., Yanase, T., Nawata, H.
  • Journal Title: Biochem Biophys Res Commun 303 Pages: 1002-1007
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aromatase in bone : roles of Vitamin D3 and androgens. (2003)
  • Author(s): Yanase, T., Suzuki, S., Goto, K., Nomura, M., Okabe, T., Takayanagi, R., Nawata, H.
  • Journal Title: J Steroid Biochem Mol Biol 86 Pages: 393-397
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments. (2003)
  • Author(s): Goto K, Zhao Y, Saito M, Tomura A, Morinaga H, Nomura M, Okabe T, Yanase T, Takayanagi, R., Nawata, H.
  • Journal Title: J Steroid Biochem Mol Biol 85 Pages: 201-208
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activin signaling through type IB activin receptor stimulates aromatase activity in the ovarian granulosa cell-like human granulosa (KGN) cells. (2003)
  • Author(s): Mukasa, C., Nomura, M., Tanaka, T., Tanaka, K., Nishi, Y., Okabe, T., Goto, K., Yanase, T., Nawata, H.
  • Journal Title: Endocrinology 144 Pages: 1603-1611
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21 (WAF1/CIP1). (2003)
  • Author(s): Mu, YM., Oba, K., Yanase, T., Ito, T., Ashida, K., Goto, K., Morinaga, H., Ikuyama, S., Takayanagi R, Nawata H.
  • Journal Title: Endocr J. 50 Pages: 771-781
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional characterization of a new human Ad4BP/SF-1 variation, G146A. (2003)
  • Author(s): WuQiang F., Yanase T., Wei L., Oba, K., Nomura M,.Okabe T, Goto, K., Nawata, H.
  • Journal Title: Biochem Biophys Res Commun. 311 Pages: 987-994
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. (2003)
  • Author(s): Lu, ZH., Mu, YM., Wang, BA., Li, XL., Lu, JM., Li, JY., Pan, CY., Yanase, T., Nawata, H.
  • Journal Title: Biochem Biophys Res Commun 303 Pages: 1002-1007
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aromatase in bone: roles of Vitamin D3 and androgens. (2003)
  • Author(s): Yanase, T., Suzuki, S., Goto, K., Nomura, M., Okabe, T., Takayanagi, R., Nawata, H.
  • Journal Title: J Steroid Biochem Mol Biol 86 Pages: 393-397
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1 ). (2003)
  • Author(s): Mu, YM., Oba, K., Yanase, T., Ito, T., Ashida, K., Goto, K., Morinaga, H., Ikuyama, S., Takayanagi R, Nawata H.
  • Journal Title: Endocr J. 50 Pages: 771-781
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional characterization of a new human Ad4BP/SF-1 variation, G146A. (2003)
  • Author(s): WuQiang F., Yanase T., Wei L., Oba, K., Nomura M., Okabe T, Goto, K., Nawata, H.
  • Journal Title: Biochem Biophys Res Commun 311 Pages: 987-994
  • Description: 「研究成果報告書概要(欧文)」より