THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC
THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC
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DOI：
10.1073/pnas.90.16.7804
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发表时间：
1993-08-15
影响因子：
11.1
通讯作者：
CLEVELAND, JL
中科院分区：
文献类型：
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作者：
BELLOFERNANDEZ, C;PACKHAM, G;CLEVELAND, JL
组成型 c-myc 表达抑制细胞周期停滞，促进进入 S 期，并导致鸟氨酸脱羧酶（ODC；EC 4.1.1.17）的生长因子独立表达。 ODC 基因在内含子 1 中包含 Myc 结合位点 CACGTG 的保守重复。在本报告中，我们证明 c-Myc 是成纤维细胞中 ODC 启动子-报告基因构建体的有效反式激活因子，需要 CACGTG 重复。这些位点赋予异源启动子构建体 Myc 反应性，表明 ODC 在转录起始水平受到 Myc 的调节。对c-myc 的缺失和点突变体的分析表明，ODC 启动子反式激活所需的结构域不包括Myc 蛋白的亮氨酸拉链。这表明Myc可能与Max以外的转录因子相互作用来反式激活ODC基因。
Constitutive c-myc expression suppresses cell cycle arrest, promotes entry into S phase, and results in the growth factor-independent expression of ornithine decarboxylase (ODC; EC 4.1.1.17). The ODC gene contains a conserved repeat of the Myc binding site, CACGTG, in intron 1. In this report, we demonstrate that c-Myc is a potent transactivator of ODC promoter-reporter gene constructs in fibroblasts that requires the CACGTG repeat. These sites conferred Myc responsiveness on heterologous promoter constructs, suggesting that ODC is regulated by Myc at the level of transcription initiation. Analysis of deletion and point mutants of c-myc revealed that domains required for transactivation of the ODC promoter did not include the leucine zipper of the Myc protein. This suggests that Myc may interact with transcription factors other than Max to transactivate the ODC gene.