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首页> 外文期刊>Molecular and Cellular Biology >Two N-myc polypeptides with distinct amino termini encoded by the second and third exons of the gene.
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Two N-myc polypeptides with distinct amino termini encoded by the second and third exons of the gene.

机译：该基因的第二和第三外显子编码具有不同氨基末端的两个N-myc多肽。

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摘要

The N-myc and c-myc genes encode closely related nuclear phosphoproteins. We found that the N-myc protein from human tumor cell lines appears as four closely migrating polypeptide bands (p58 to p64) in sodium dodecyl sulfate-polyacrylamide gels. This and the recent finding that the c-myc protein is synthesized from two translational initiation sites located in the first and second exons of the gene (S. R. Hann, M. W. King, D. L. Bentley, C. W. Anderson, and R. N. Eisenman, Cell 52:185-195, 1988) prompted us to study the molecular basis of the N-myc protein heterogeneity. Dephosphorylation by alkaline phosphatase reduced the four polypeptide bands to a doublet with an electrophoretic mobility corresponding to the two faster-migrating N-myc polypeptides (p58 and p60). When expressed transiently in COS cells, an N-myc deletion construct lacking the first exon produced polypeptides similar to the wild-type N-myc protein, indicating that the first exon of the N-myc gene is noncoding. Furthermore, mutants deleted of up to two thirds of C-terminal coding domains still retained the capacity to produce a doublet of polypeptides, suggesting distinct amino termini for the two N-myc polypeptides. The amino-terminal primary structure of the N-myc protein was studied by site-specific point mutagenesis of the 5' end of the long open reading frame and by N-terminal radiosequencing of the two polypeptides. Our results show that the N-myc polypeptides are initiated from two alternative in-phase AUG codons located 24 base pairs apart at the 5' end of the second exon. Both of these polypeptides are phosphorylated and localized to the nucleus even when expressed separately. Interestingly, DNA rearrangements activating the c-myc gene are often found in the 1.7-kilobase-pair region between the two c-myc translational initiation sites and correlate with the loss of the longer c-myc polypeptide. Thus the close spacing of the two N-myc initiation codons could explain the relative resistance of the N-myc gene to similar modes of oncogenic activation.
机译：N-myc和c-myc基因编码紧密相关的核磷蛋白。我们发现，来自人肿瘤细胞系的N-myc蛋白在十二烷基硫酸钠-聚丙烯酰胺凝胶中显示为四个紧密迁移的多肽带（p58至p64）。最近发现的c-myc蛋白是由位于该基因第一个和第二个外显子的两个翻译起始位点合成的（SR Hann，MW King，DL Bentley，CW Anderson和RN Eisenman，Cell 52：185- 195，1988）促使我们研究N-myc蛋白异质性的分子基础。碱性磷酸酶进行的去磷酸化作用将四个多肽条带还原为双峰，其电泳迁移率对应于两个较快迁移的N-myc多肽（p58和p60）。当在COS细胞中瞬时表达时，缺少第一个外显子的N-myc缺失构建体会产生类似于野生型N-myc蛋白的多肽，这表明N-myc基因的第一个外显子是非编码的。此外，缺失了多达三分之二的C-末端编码域的突变体仍然保留了产生多肽的二重体的能力，这暗示了两种N-myc多肽的独特氨基末端。 N-myc蛋白的氨基末端一级结构通过长开放阅读框5'端的位点特异性诱变和两种多肽的N端放射性测序研究。我们的结果表明，N-myc多肽由位于第二个外显子5'末端相距24个碱基对的两个备选同相AUG密码子引发。这些多肽都被磷酸化并定位在细胞核上，即使单独表达也是如此。有趣的是，经常在两个c-myc翻译起始位点之间的1.7碱基对区域发现激活c-myc基因的DNA重排，并且与更长的c-myc多肽的丢失有关。因此，两个N-myc起始密码子的紧密间隔可以解释N-myc基因对类似的致癌激活方式的相对抗性。

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