LUCA15, a putative tumour suppressor gene encoding an RNA-binding nuclear protein, is down-regulated in ras-transformed Rat-1 cells
LUCA15, a putative tumour suppressor gene encoding an RNA-binding nuclear protein, is down-regulated in ras-transformed Rat-1 cells
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DOI：
10.1046/j.1365-2443.2000.00370.x
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发表时间：
2000-10-01
期刊：
影响因子：
2.1
通讯作者：
Itoh, H
中科院分区：
文献类型：
--
作者：
Edamatsu, H;Kaziro, Y;Itoh, H
背景：哺乳动物细胞的增殖受多种细胞内促有丝分裂信号通路控制。在细胞内途径中，Ras参与原癌基因如即刻早期基因c-fos的激活。在肿瘤中发现了ras基因的体细胞突变，其引起Ras的组成性激活。虽然这些研究结果表明，Ras介导的通路的组成性激活改变了一组基因的表达，涉及肿瘤发生，这些基因尚未完全studied.Results：要研究的上调或下调基因在Ras转化的细胞，我们分析了大鼠-1转染表达Ras（G12 V）突变蛋白的异丙基-1-β-硫代-D-半乳糖苷使用的差异显示。我们发现，大鼠同系物LUCA 15，这已被克隆最初作为一个假定的肿瘤抑制基因定位在人类3号染色体上，下调Ras（G12 V）的表达的mRNA水平。表位标记的LUCA 15蛋白定位于细胞核中，并具有体外结合聚（G）RNA均聚物的能力。结论：LUCA 15是ras基因转染后细胞中表达下调的基因之一，提示LUCA 15可能通过其mRNA水平的改变对细胞增殖起负调控作用。
Background: The proliferation of mammalian cells is controlled by various intracellular mitogenic signalling pathways. In the intracellular pathways, Ras is involved in the activation of proto-oncogenes such as an immediate early gene c-fos. The somatic mutations of ras genes that elicit the constitutive activation of Ras have been found in tumours. Although these findings suggest that the constitutive activation of Ras-mediated pathways alters the expression of a set of genes involving tumorigenesis, these genes have not yet fully been studied.Results: To study the up- or down-regulated genes in ras-transformed cells, we analysed Rat-1 transfectants expressing Ras(G12V) mutant protein in response to isopropyl-1-beta-thio-D-galactoside using a differential display. We found that the mRNA level of rat homologue of LUCA15, which has been cloned initially as a putative tumour suppressor gene mapped on human chromosome 3, was down-regulated by the expression of Ras(G12V). Epitope-tagged LUCA15 protein was localized in nuclei and had the ability to bind poly(G) RNA homopolymers in vitro. Moreover, ectopic expression of LUCA15 in human fibrosarcoma HT1080 cells suppressed the cell growth.Conclusion: These results demonstrate that LUCA15 is one of the down-regulated genes in ras-transformed cells, and suggests that LUCA15 may function as a negative regulator of cell proliferation by the alteration of its mRNA level.