Analysis of the androgen response element of mouse EGF gene by use of the androgen receptor expressed in Echerichia coli

利用大肠杆菌表达的雄激素受体分析小鼠EGF基因的雄激素反应元件

基本信息

  • 批准号:
    06807144
  • 负责人:
  • 金额:
    $ 1.09万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
  • 财政年份:
    1994
  • 资助国家:
    日本
  • 起止时间:
    1994 至 1995
  • 项目状态:
    已结题

项目摘要

We studied the action mechanism of androgen in the mouse submandibular gland that shows the typical sexual dimorphism. To prepare the adsorbent specifically interacting with potential androgen response element, the DNA-domain of human androgen receptor (ARDBD) was expressed in E.coli. ARDBD fused to glutathione S-transferase (GST) existed as a dimer via GST-GST interaction and had a high affinity for mouse mammary tumor virus DNA.However, elimination of GST mojety by thrombin cleavage caused the reduction of the binding affinity, indicating that the dimerization of ARDBD is essential for the DNA binding of high affinity. The affinity column with GST-ARDBD was incubated with DNA fragments derived from 5'-upstream region of mouse EGF gene promoter. The column specifically trapped the 130 bp fragment located at -727- -598b of EGF gene. Comparison of the sequence with those of androgen-dependent androgen genes revealed the segment homologous among these genes.The effect of testosterone on the expression of AR mRNA in mouse submandibular glands was examined. The AR mRNA level was higher in females than in males. Castration resulted in elevation of the level, while testosterone injection to female mice caused the reduction. Thses results show that the AR mRNA level is down-regulated by testosterone.We finally investigated the mechanism of dimerization of the 90-kDa heat shock protein (HSP90), a binding component of steroid receptors. The dimeric structure of HSP90alpha is mediated by the C-terminal 191 amino acids and consists of duplicate interactions of the C-terminal region (Met628/Ala629-Asp732) of one subunit and the adjacent more N-terminal region (Val542-Tyr627/Met628) of the other subunit. The amino acids 290-732 were sufficient for the interaction with steroid receptors.
我们研究了雄激素在表现典型性二型性的小鼠颌下腺中的作用机制。为了制备与潜在雄激素反应元件特异结合的吸附剂,在大肠杆菌中表达了人雄激素受体(ARDBD)的DNA结构域。与谷胱甘肽S转移酶(GST)融合的ARDBD通过GST-GST相互作用以二聚体的形式存在,与小鼠乳腺肿瘤病毒DNA具有较高的亲和力,但凝血酶切割消除GST部分会导致结合亲和力降低,表明ARDBD的二聚化是高亲和力结合DNA所必需的。GST-ARDBD亲和层析柱与小鼠EGF基因启动子5‘-上游区DNA片段温育。该柱特异性捕获了EGF基因-727--598b处的130个碱基片段。将该序列与雄激素依赖性雄激素基因的序列进行比较,发现这些基因的片段具有同源性。AR基因表达水平女性高于男性。去势会导致水平升高,而雌性小鼠注射睾丸素会导致水平下降。这些结果表明,睾酮下调了AR的mRNA水平。最后,我们研究了类固醇受体结合成分90-kDa热休克蛋白(HSP90)的二聚化机制。HSP90α的二聚体结构由191个氨基酸组成,由一个亚基的C-末端区域(Met628/Ala629-Asp732)和另一个亚基相邻的多个N-末端区域(Val542-Tyr627/Met628)重复相互作用组成。290-732位氨基酸足以与类固醇受体相互作用。

项目成果

期刊论文数量(58)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nemoto, T. et al.: "Mechanism of dimer formation of the 90-kDa heat shock protein." Eur. J. Biochem.223. 1-8 (1995)
Nemoto, T. 等人:“90-kDa 热休克蛋白二聚体形成机制。”
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    0
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Ema, M. et al.: "Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21." J. Biochem.116. 845-851 (1994)
Ema, M. 等人:“人类芳基烃受体:功能表达和 7p21 染色体分配。”
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    0
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Kyakumoto, S., Nemoto, T., Hoshino, M and Ota, M.: "Expression of RXR family in human salivary gland adenocarcinoma cell line HSG" Jpn.J.Tissue Cult.Dent.Res.4 (Japanese). 55-65 (1995)
Kyakumoto, S.、Nemoto, T.、Hoshino, M 和 Ota, M.:“RXR 家族在人唾液腺腺癌细胞系 HSG 中的表达”Jpn.J.Tissue Cult.Dent.Res.4(日语)。
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  • 影响因子:
    0
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Nemoto, T., Matsusaka, T., Ota, M., Ohara-Nemoto, Y., Kaneko, M., Horigome, T.and Inano, K.: "Kinship between self-oligomerization and the estrogen receptor-interacting activities of the 90-kDa heat shock protein" Steroid Biochem. (Life Sci.Adv.). (in pre
Nemoto, T.、Matsusaka, T.、Ota, M.、Ohara-Nemoto, Y.、Kaneko, M.、Horigome, T. 和 Inano, K.:“自我寡聚化与雌激素受体相互作用活性之间的亲缘关系
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  • 影响因子:
    0
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Nemoto, T., Ota, M., Ohara-Nemoto Y., and M.Kaneko: "Identification of proteins by use of glutathione S-transferase fusion system" Anal.Biochem.227. 396-399 (1995)
Nemoto, T.、Ota, M.、Ohara-Nemoto Y. 和 M.Kaneko:“利用谷胱甘肽 S-转移酶融合系统鉴定蛋白质”Anal.Biochem.227。
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NEMOTO Takayuki其他文献

NEMOTO Takayuki的其他文献

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{{ truncateString('NEMOTO Takayuki', 18)}}的其他基金

Exopeptidases from periodontopathic bacteria as risk factors of type-2 diabetes mellitus
牙周病细菌的外肽酶作为 2 型糖尿病的危险因素
  • 批准号:
    15K11047
  • 财政年份:
    2015
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanism of novel peptide metabolism system in periodontophatic bacterium
牙周病菌新型肽代谢系统的机制
  • 批准号:
    24592809
  • 财政年份:
    2012
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clarification of insulin/IGF-I receptor signal expression mechanism
阐明胰岛素/IGF-I受体信号表达机制
  • 批准号:
    21790244
  • 财政年份:
    2009
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Therapeutic Establishment for Gingival Hyperplasia and Scar Formation by Use of Collagen-Digestible Proteases
使用胶原蛋白消化蛋白酶治疗牙龈增生和疤痕形成的治疗方法的建立
  • 批准号:
    21592367
  • 财政年份:
    2009
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Collagen processing and molecular chaperones : molecular anatomy based on the domain structures
胶原蛋白加工和分子伴侣:基于域结构的分子解剖学
  • 批准号:
    13671943
  • 财政年份:
    2001
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Domain structure, expressional regulation and autoimmunity of HSP90
HSP90的结构域结构、表达调控和自身免疫
  • 批准号:
    10671746
  • 财政年份:
    1998
  • 资助金额:
    $ 1.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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Androgen receptor: A master regulator of lipid metabolism
雄激素受体:脂质代谢的主要调节因子
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    DP230103210
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    2023
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    $ 1.09万
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Regulation of androgen receptor signaling in prostate cancer by protein arginine methylation
通过蛋白质精氨酸甲基化调节前列腺癌中的雄激素受体信号传导
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    10584689
  • 财政年份:
    2023
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Structural and functional analysis of a novel class of androgen receptor antagonists
一类新型雄激素受体拮抗剂的结构和功能分析
  • 批准号:
    10650956
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    2023
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Role of the Androgen Receptor in Insulin Secretion in the Male
雄激素受体在男性胰岛素分泌中的作用
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    10488954
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    2023
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Targeting tumor cell macrophage lipid interactions to overcome resistance to androgen receptor targeted therapy
靶向肿瘤细胞巨噬细胞脂质相互作用以克服对雄激素受体靶向治疗的耐药性
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    10651105
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    2023
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Preclinical development of ONCT-505, an Androgen Receptor Antagonist and Degrader, as new potential therapeutic for Kennedy's Disease
ONCT-505(一种雄激素受体拮抗剂和降解剂)的临床前开发,作为肯尼迪病的新潜在治疗方法
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    10603636
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    2023
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Androgen receptor function in melanoma
雄激素受体在黑色素瘤中的功能
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    10416658
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Proliferating cell nuclear antigen in regulation of androgen receptor signalings in castration-resistant prostate cancer cells
增殖细胞核抗原对去势抵抗性前列腺癌细胞雄激素受体信号传导的调节
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Effects of androgen receptor (AR) signaling on CD4+ T cell metabolism during airway inflammation
气道炎症期间雄激素受体 (AR) 信号对 CD4 T 细胞代谢的影响
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    10534943
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    $ 1.09万
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TITLE: BLADDER CANCER CHEMOPREVENTION USING THE ANDROGEN RECEPTOR INHIBITOR APALUTAMIDE
标题:使用雄激素受体抑制剂阿帕鲁胺进行膀胱癌化学预防
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