A novel c-Myc-responsive gene, JPO1, participates in neoplastic transformation
A novel c-Myc-responsive gene, JPO1, participates in neoplastic transformation
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DOI：
10.1074/jbc.m107357200
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发表时间：
2001-12-21
影响因子：
4.8
通讯作者：
Dang, CV
中科院分区：
文献类型：
--
作者：
Prescott, JE;Osthus, RC;Dang, CV
通过代表性差异分析，我们发现了一个新的c- myc应答基因，命名为JPO1。JPO1响应两种可诱导的c-Myc系统，并作为c-Myc的直接靶基因。JPO1 mRNA的表达在胸腺、小肠和结肠中很容易检测到，而在脾脏、骨髓和外周白细胞中的表达相对较低。我们克隆了一个全长的JPO1 cDNA，编码一个47kda的核蛋白。为了确定JPO1在myc介导的细胞表型中的作用，我们检测了稳定的过表达JPO1的Rat1a成纤维细胞，并与转化的Rat1a- myc细胞进行了比较。尽管与c-Myc相比，JPO1的转化活性降低，但在Rat1a转化试验中，JPO1补充了有转化缺陷的My-c Box II突变体。这种互补为c-Myc和JPO1之间的遗传联系提供了证据。与c-Myc类似，在甲基纤维素检测中，JPO1过表达增强了CB33人淋巴母细胞样细胞的克隆原性。这些观察结果表明，JPO1参与了c-Myc介导的转化，支持了一个新兴的概念，即c-Myc靶基因构成了从c-Myc到各种myc相关表型并最终导致肿瘤发生的通路网络中的节点。
We have identified a novel c-Myc-responsive gene, named JPO1, by representational difference analysis. JPO1 responds to two inducible c-Myc systems and behaves as a direct c-Myc target gene. JPO1 mRNA expression is readily detectable in the thymus, small intestine, and colon, whereas expression is relatively low in spleen, bone marrow, and peripheral leukocytes. We cloned a full-length JPO1 cDNA that encodes a 47-kDa nuclear protein. To determine the role of JPO1 in Myc-mediated cellular phenotypes, stable Rat1a fibroblasts overexpressing JPO1 were tested and compared with transformed Rat1a-Myc cells. Although JPO1 has a diminished transforming activity as compared with c-Myc, JPO1 complements a transformation-defective My-c Box II mutant in the Rat1a transformation assay. This complementation provides evidence for a genetic link between c-Myc and JPO1. Similar to c-Myc, JPO1 overexpression enhances the clonogenicity of CB33 human lymphoblastoid cells in methylcellulose assays. These observations suggest that JPO1 participates in c-Myc-mediated transformation, supporting an emerging concept that c-Myc target genes constitute nodal points in a network of pathways that lead from c-Myc to various Myc-related phenotypes and ultimately to tumorigenesis.