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Significance of hnRNP A2/B1 proteins in lung cancer

Significance of hnRNP A2/B1 proteins in lung cancer
hnRNP A2/B1 蛋白在肺癌中的意义
批准号:
11670564
负责人:
SATOH Hiroaki
金额:
$2.18万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000

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中文摘要
翻译
异质核核糖核蛋白(hnRNP) A2/B1是参与RNA前加工的核RNA结合蛋白。据报道,A2/B1的过表达对于早期发现癌症是有用的。首先,我们利用合成的肽段作为免疫原生成抗a2单克隆抗体4G8。我们独创的抗A2/B1单克隆抗体,包括4G8,能够分别识别A2和B1,其特异性为研究A2和B1的生化和功能特性提供了依据。这些抗体显示A2和B1在细胞内分布和细胞周期代谢方面存在差异。A2/B1蛋白已被报道与三聚体DNA重复序列结合。B1和B0b是B1的次要同工型之一,与A2和BOa相比,B1和B0b对端粒单链DNA (ssDNA)具有更高的亲和力。用纯化的B1和B0b进行动力学分析表明,它们与单一的三聚体重复序列相互作用。功能分析表明B1和B0b以串联方式与三聚体重复序列结合,保护它们免受核酸酶的侵害,并促进端粒酶的活性。转基因小鼠呼吸系统未见明显变化,但精子发生异常。因此,我们将研究hnRNP A2/B1与异常的关系。
英文摘要
Hetrogenous nuclear ribonucleoprotein (hnRNP) A2/B1 are nuclear RNA binding proteins involved in pre-RNA processing. It has been reported that the overexpression, of A2/B1, is useful for detecting cancers in early stage. First, we generated an anti-A2 monoclonal antibody 4G8 using the synthetic peptide as an immunogen. Our original anti-A2/B1 monoclonal antibodies including 4G8 could separately recognized A2 and B1, and their specificity made them useful in the study of the biochemical and functional properties of A2 and B1. These antibodies have demonstrated differences between A2 and B1 in the intracellular distribution and in the metabolism through cell cycles.A2/B1 proteins have been reported to bind teromeric DNA repeats. B1 and B0b, which is one of the minor isoforms of B1, were suggested to have higher affinities to telomeric single-strand DNA (ssDNA) than A2 and BOa. Kinetic analyses using purified B1 and B0b indicated that they interact with a single array of teromeric repeats. Functional assays demonstrated that B1 and B0b bind with teromeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity.Transgenic mice did not show any changes in respiratory system, however, spermatogenetic abnormality was found in the mice. Therefore, we will research the relationship between hnRNP A2/B1 and the abnormality.
期刊论文(15)
专著(0)
科研奖励(0)
会议论文
Satoh H. et al.: "Expression of hnRNP A2/B1 proteins in human cancer cell lines."International Journal of Oncology. 16. 763-767 (2000)
Satoh H.等人:“hnRNP A2/B1蛋白在人类癌细胞系中的表达。”国际肿瘤学杂志。
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通讯作者:
Makoto Hamasaki, Hiroshi Kamma, Wen Wen Wu, Setsuko Kaneko, Masachika Fujiwara, Hiroaki Satoh, Seiji Haraoka, Masahiro Kikuchi, Takayuki Shirakusa.: "Expression of hnRNP B1 in four major histological types of lung cancers."Anticancer Res. (in press).
Makoto Hamasaki、Hiroshi Kamma、Wen Wen Wu、Setsuko Kaneko、Masachika Fujiwara、Hiroaki Satoh、Seiji Haraoka、Masahiro Kikuchi、Takayuki Shirakusa.:“hnRNP B1 在四种主要组织学类型肺癌中的表达。”抗癌研究。
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通讯作者:
Kamma H,et al.: "Molecular characterization of the hnRNP A2/B1 proteins: tissue specific expreaion and novel isoforms"Exp.Cell.Res.. 246. 399-411 (1999)
Kamma H 等人:“hnRNP A2/B1 蛋白的分子特征:组织特异性表达和新亚型”Exp.Cell.Res.. 246. 399-411 (1999)
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通讯作者:
Satoh H,et al.: "Expression of hnRNP A2/B1 proteins in human cancer cell lines."Int.J.Oncol.. 16(in press). (2000)
Satoh H 等人:“人类癌细胞系中 hnRNP A2/B1 蛋白的表达”。Int.J.Oncol.. 16(出版中)。
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