THE PROTEIN ENCODED BY THE HUMAN PROTO-ONCOGENE C-MYC
THE PROTEIN ENCODED BY THE HUMAN PROTO-ONCOGENE C-MYC
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DOI：
10.1073/pnas.81.24.7742
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
BISHOP, JM
中科院分区：
文献类型：
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作者：
RAMSAY, G;EVAN, GI;BISHOP, JM
原癌基因c-myc可能在控制正常细胞的生长和分裂中起作用，并且该基因的异常已经与多种人类肿瘤的发生有关。为了促进对这些问题的进一步研究，开发了允许鉴定和分离由人类和其他哺乳动物形式的c-myc编码的蛋白质的抗血清。c-myc（人）产生至少2种表观分子量为62，000 [pp 62 c-myc（人），主要产物]和66，000 [pp 66 c-myc（人），产生的量较小，可能是分子量为62，000的蛋白质的修饰形式]的磷蛋白。两种蛋白质都具有相对较短的半衰期，约小鼠c-myc编码类似的蛋白质，分子量为64，000和66，000。通过DNA介导的基因转移转化的细胞的使用支持了先前的推论，即c-myc（人）的整个编码结构域包含在基因的第2和第3外显子中，并通过显示类似的外显子指定c-myc（鸡）的整个蛋白质产物来解决先前的模糊性。含有扩增的c-myc（人）的肿瘤细胞产生相对大量的pp 62/pp 66 c-myc（人）。相比之下，在伯基特淋巴瘤细胞中发现的c-myc易位似乎只是维持c-myc（人类）的表达水平，而不是将该基因的表达增加到明显异常的水平。
The proto-oncogene c-myc may play a role in controlling the growth and division of normal cells, and abnormalities of the gene have been implicated in the genesis of a substantial variety of human tumors. To facilitate further study of these issues, antisera were developed that permit the identification and isolation of the protein encoded by the human and other mammalian versions of c-myc. c-myc (human) gives rise to at least 2 phosphoproteins with apparent MW of 62,000 [pp62c-myc(human), the major product] and 66,000 [pp66c-myc(human), produced in smaller quantities and possibly a modified version of the MW 62,000 protein]. Both proteins have relatively short half-lives of .apprxeq. 30 min. Mouse c-myc encodes similar proteins with MW of 64,000 and 66,000. The use of cells transformed by DNA-mediated gene transfer sustained previous deductions that the entire coding domain of c-myc (human) is contained in the 2nd and 3rd exons of the gene and resolved previous ambiguities by showing that analogous exons specify the entire protein product of c-myc(chicken). Tumor cells containing amplification of c-myc (human) produce relatively large amounts of pp62/pp66c-myc(human). By contrast, translocations of c-myc found in cells derived from Burkitt lymphoma appear merely to sustain expression of c-myc (human) at levels found also in nontumorigenic lymphoblastoid cells, rather than to increase expression of the gene to manifestly abnormal levels.