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首页> 外文期刊>Molecular and Cellular Biology >Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins.
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Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins.

机译：鉴定下游启动的c-Myc蛋白，它们是全长c-Myc蛋白反式激活的显性负抑制剂。

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The c-myc gene has been implicated in multiple cellular processes including proliferation, differentiation, and apoptosis. In addition to the full-length c-Myc 1 and 2 proteins, we have found that human, murine, and avian cells express smaller c-Myc proteins arising from translational initiation at conserved downstream AUG codons. These c-Myc short (c-Myc S) proteins lack most of the N-terminal transactivation domain but retain the C-terminal protein dimerization and DNA binding domains. As with full-length c-Myc proteins, the c-Myc S proteins appear to be localized to the nucleus, are relatively unstable, and are phosphorylated. Significant levels of c-Myc S, often approaching the levels of full-length c-Myc, are transiently observed during the rapid growth phase of several different types of cells. Optimization of the upstream initiation codons resulted in greatly reduced synthesis of the c-Myc S proteins, suggesting that a "leaky scanning" mechanism leads to the translation of these proteins. In some hematopoietic tumor cell lines having altered c-myc genes, the c-Myc S proteins are constitutively expressed at levels equivalent to that of full-length c-Myc. As predicted, the c-Myc S proteins are unable to activate transcription and inhibited transactivation by full-length c-Myc proteins, suggesting a dominant-negative inhibitory function. While these transcriptional inhibitors would not be expected to function as full-length c-Myc, the occurrence of tumors which express constitutive high levels of c-Myc S and their transient synthesis during rapid cell growth suggest that these proteins do not interfere with the growth-promoting functions of full-length c-Myc.
机译：c-myc基因与多种细胞过程有关，包括增殖，分化和凋亡。除了全长c-Myc 1和2蛋白外，我们还发现人，鼠和禽细胞表达较小的c-Myc蛋白，这些蛋白是由保守下游AUG密码子的翻译起始产生的。这些c-Myc短（c-Myc S）蛋白缺少大多数N端反式激活结构域，但保留了C端蛋白二聚化和DNA结合结构域。与全长c-Myc蛋白一样，c-Myc S蛋白似乎位于细胞核内，相对不稳定，并被磷酸化。在几种不同类型细胞的快速生长阶段，瞬时观察到大量的c-Myc S水平，经常接近全长c-Myc水平。上游起始密码子的优化导致c-Myc S蛋白的合成大大减少，这表明“泄漏扫描”机制导致这些蛋白的翻译。在一些具有改变的c-myc基因的造血肿瘤细胞系中，c-Myc S蛋白以等同于全长c-Myc水平的水平组成性表达。如所预测的，c-Myc S蛋白不能激活转录，并不能抑制全长c-Myc蛋白的反式激活，这提示了显性负抑制功能。虽然预期这些转录抑制剂不会发挥全长c-Myc的功能，但表达高水平c-Myc S的肿瘤的发生及其在细胞快速生长过程中的短暂合成提示这些蛋白质不会干扰生长促进全长c-Myc的功能。

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