Schreiber-Agus N, Torres R, Horner J, Lau A, Jamrich M, DePinho R A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
Mol Cell Biol. 1993 Apr;13(4):2456-68. doi: 10.1128/mcb.13.4.2456-2468.1993.
A polymerase chain reaction-based cloning strategy allowed for the isolation of two distinct Xenopus L-myc genes, as well as previously isolated xc- and xN-myc genes, thus demonstrating that these three well-defined members of the mammalian myc gene family are present in lower vertebrates as well. Comparison of the Xenopus and mammalian Myc families revealed a high degree of structural relatedness at the gene and protein levels; this homology was consistent with the ability of the xc-myc1 and xN-myc1 genes to function as oncogenes in primary mammalian cells. In contrast, the xL-myc1 gene was found to be incapable of transforming rat embryo fibroblast cells, and this inactivity may relate to localized but significant differences in its putative transactivation domain. Analysis of xc-, xN-, and xL-myc gene expression demonstrated that (i) all three genes were highly expressed during oogenesis and their transcripts accumulated as abundant maternal mRNAs, (ii) each gene exhibited a distinctive pattern of expression during embryogenesis and in adult tissues, and (iii) the xL-myc1 and xL-myc2 genes were coordinately expressed in the maternal and zygotic genomes. The markedly high expression of the Xenopus myc gene family in differentiated tissues, such as the central nervous system and kidney, contrasts sharply with the low levels observed in mammalian adult tissues. These differences may reflect unique functions of the Myc family proteins in processes specific to amphibians, such as tissue regeneration.
基于聚合酶链反应的克隆策略使得两个不同的非洲爪蟾L-myc基因以及先前分离出的xc-和xN-myc基因得以分离,从而证明哺乳动物myc基因家族这三个明确的成员在低等脊椎动物中也存在。对非洲爪蟾和哺乳动物Myc家族的比较揭示了在基因和蛋白质水平上高度的结构相关性;这种同源性与xc-myc1和xN-myc1基因在原代哺乳动物细胞中作为癌基因发挥作用的能力相一致。相比之下,发现xL-myc1基因无法转化大鼠胚胎成纤维细胞,这种无活性可能与其假定的反式激活结构域中局部但显著的差异有关。对xc-、xN-和xL-myc基因表达的分析表明:(i)所有这三个基因在卵子发生过程中高度表达,其转录本作为丰富的母源mRNA积累;(ii)每个基因在胚胎发育过程中和成年组织中表现出独特的表达模式;(iii)xL-myc1和xL-myc2基因在母源和合子基因组中协同表达。非洲爪蟾myc基因家族在分化组织(如中枢神经系统和肾脏)中的显著高表达与在哺乳动物成年组织中观察到的低水平形成鲜明对比。这些差异可能反映了Myc家族蛋白在两栖动物特有的过程(如组织再生)中的独特功能。