JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity
JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity
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DOI：
10.1016/j.bbaexp.2006.02.004
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Yoshida, Kenichi
中科院分区：
文献类型：
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作者：
Goto, Yuya;Hayashi, Reiko;Yoshida, Kenichi
JPO1/CDCA7最初被认为是参与肿瘤转化的c-Myc反应基因。在这里，我们报告了JP01/CDCA7作为转录因子E2F1的直接转录靶点的鉴定。我们证明，通过腺病毒介导的基因转移过表达E2F1上调了人细胞中JPO1/CDCA7的mRNA表达。对人和小鼠JPO1/CDCA7启动子结构的分析表明，E2F反应序列是E2F1诱导JPO1/CDCA7基因转录激活所必需的。在E2F家族成员中，E2F1到E2F4，而不是E2F5或E2F6，激活了JPO1/CDCA7报告结构。染色质免疫沉淀分析表明，E2F1、E2F2和E2F4与人POP CDCA7基因的E2F反应序列特异性结合。与JPO2/R1一样，JPO1/CDCA7蛋白的C端富含半胱氨酸区域在哺乳动物单杂交实验中诱导转录活性。综上所述，我们的结果表明，JPO1/CDCA7是一种独特的转录调节因子，其表达可被E2F1和c-Myc激活。(C)2006爱思唯尔B.V.保留所有权利。
JPO1/CDCA7 was originally identified as a c-Myc-responsive gene that participates in neoplastic transformation. Here, we report the identification of JP01/CDCA7 as a direct transcriptional target of transcription factor E2F1. We demonstrated that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated JPO1/CDCA7 mRNA expression in human cells. Analysis of human and mouse JPO1/CDCA7 promoter constructs showed that an E2F-responsive sequence was necessary for E2F1-induced activation of the JPO1/CDCA7 gene transcription. Among the members of the E2F family, E2F1 to E2F4, but not E2F5 or E2F6, activated the JPO1/CDCA7 reporter construct. Chromatin immunoprecipitation analysis demonstrated that E2F1, E2F2, and E2F4 specifically bound to an E2F-responsive sequence of the human POP CDCA7 gene. Like JPO2/R1, which has a homologous transcriptional regulator domain, the C-terminal cysteine-rich region of JPO1/CDCA7 protein induced transcriptional activity in a mammalian one-hybrid assay. Taken together, our results suggest that JPO1/CDCA7 is a unique transcription regulator whose expression is activated by E2F1 as well as c-Myc. (c) 2006 Elsevier B.V. All rights reserved.