Hann S R, Sloan-Brown K, Spotts G D
Department of Cell Biology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-2175.
Genes Dev. 1992 Jul;6(7):1229-40. doi: 10.1101/gad.6.7.1229.
c-myc belongs to a small, yet growing, group of eukaryotic mRNAs that initiate translation inefficiently from a non-AUG codon upstream from a more efficient AUG codon. We have examined the translational regulation of non-AUG-initiated c-myc 1 and AUG-initiated c-myc 2 protein synthesis in avian and mouse cells during proliferation. As lymphoid, erythroid, and embryo fibroblast cells approached high densities in culture, there was a sustained 5- to 10-fold induction in the synthesis of c-myc 1 protein to levels greater than or equal to c-myc 2 protein synthesis. Treatment with conditioned/depleted media from high-density cells was able to reproduce this activation in low-density cells within 5 hr. Additional studies with the conditioned/depleted media revealed that amino acid availability, specifically methionine deprivation, was responsible for this unique translational control. Our results describe a specific and dramatic regulation of dual translational initiation. Furthermore, these results represent a novel translational activation of a specific gene in higher eukaryotes in response to nutrient deprivation.
c-myc属于一小群但数量不断增加的真核生物mRNA，它们从一个效率更高的AUG密码子上游的非AUG密码子开始进行低效翻译。我们研究了在增殖过程中禽细胞和小鼠细胞中非AUG起始的c-myc 1和AUG起始的c-myc 2蛋白质合成的翻译调控。随着淋巴细胞、红细胞和胚胎成纤维细胞在培养中接近高密度，c-myc 1蛋白的合成持续诱导5至10倍，达到大于或等于c-myc 2蛋白合成的水平。用来自高密度细胞的条件/耗尽培养基处理能够在5小时内在低密度细胞中重现这种激活。对条件/耗尽培养基的进一步研究表明，氨基酸可用性，特别是蛋氨酸剥夺，是这种独特翻译控制的原因。我们的结果描述了双重翻译起始的特异性和显著调控。此外，这些结果代表了高等真核生物中特定基因响应营养剥夺的一种新型翻译激活。
