Hann S R, Dixit M, Sears R C, Sealy L
Department of Cell Biology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-2175.
Genes Dev. 1994 Oct 15;8(20):2441-52. doi: 10.1101/gad.8.20.2441.
The myc proto-oncogene family has been implicated in multiple cellular processes, including proliferation, differentiation, and apoptosis. The Myc proteins, as heterodimers with Max protein, have been shown to function as activators of transcription through an E-box DNA-binding element, CACGTG. We have now found that the c-Myc proteins regulate transcription through another, noncanonical, DNA sequence. The non-AUG-initiated form of the c-Myc protein, c-Myc 1, strongly and specifically activates transcription of the C/EBP sequences within the EFII enhancer element of the Rous sarcoma virus long terminal repeat. In contrast, comparable amounts of the AUG-initiated form, c-Myc 2, fail to significantly affect enhancer activity. However, both c-Myc proteins trans-activate the CACGTG sequence comparably. In addition, Myc/Max heterodimers, but not Max homodimers, bind to the EFII enhancer sequence in vitro. Finally, c-Myc 1 overexpression, but not c-Myc 2 overexpression, significantly inhibits cell growth. These results reveal new transcriptional activities for the Myc proteins and demonstrate that the different forms of the Myc protein are functionally distinct. These results also suggest an interplay between two different growth regulatory transcription factor families.
myc原癌基因家族与多种细胞过程有关，包括增殖、分化和凋亡。Myc蛋白与Max蛋白形成异二聚体，已被证明可通过E盒DNA结合元件CACGTG作为转录激活因子发挥作用。我们现在发现，c-Myc蛋白通过另一种非经典的DNA序列调节转录。c-Myc蛋白的非AUG起始形式c-Myc 1强烈且特异性地激活劳斯肉瘤病毒长末端重复序列的EFII增强子元件内C/EBP序列的转录。相比之下，等量的AUG起始形式c-Myc 2未能显著影响增强子活性。然而，两种c-Myc蛋白对CACGTG序列的反式激活作用相当。此外，Myc/Max异二聚体而非Max同二聚体在体外与EFII增强子序列结合。最后，c-Myc 1的过表达而非c-Myc 2的过表达显著抑制细胞生长。这些结果揭示了Myc蛋白新的转录活性，并证明Myc蛋白的不同形式在功能上是不同的。这些结果还表明两个不同的生长调节转录因子家族之间存在相互作用。
