BIOLOGICAL PROPERTIES OF HUMAN C-HA-RAS 1 GENES MUTATED AT CODON-12
BIOLOGICAL PROPERTIES OF HUMAN C-HA-RAS 1 GENES MUTATED AT CODON-12
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DOI：
10.1038/312071a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
LEVINSON, AD
中科院分区：
文献类型：
--
作者：
SEEBURG, PH;COLBY, WW;LEVINSON, AD
脊椎动物基因组包含原癌基因，其表达增强或突变改变似乎与自然发生的肿瘤的发生有关1，2。这些激活的基因，通常通过它们诱导NIH 3 T3细胞恶性转化的能力来检测，通常与Harvey（Ha-ras）11或Kirsten（Ki-ras）12小鼠肉瘤病毒的癌基因3 - 10或该家族的第三个成员（N-ras）13-15相关。激活涉及点突变，其通常影响编码的21，000分子量多肽（p21）的密码子12（参考文献16-26）。为了深入了解p21激活所涉及的结构要求，我们现在已经构建了20个突变c-Ha-ras 1基因体外诱变，每个编码不同的氨基酸密码子12。用这些改变的基因转染的大鼠成纤维细胞的分析表明，除了甘氨酸（由正常的细胞色素基因编码）和12位的脯氨酸外，所有氨基酸都能激活p21，这表明在多肽的这一区域需要α-螺旋结构。然而，被激活的基因转化的细胞的形态表型可以取决于该位置处的特定氨基酸。
Vertebrate genomes contain proto-oncogenes whose enhanced expression or alteration by mutation seems to be involved in the development of naturally occurring tumours1,2. These activated genes, usually assayed by their ability to induce the malignant transformation of NIH 3T3 cells, are frequently related to therasoncogene3–10of Harvey (Ha-ras)11or Kirsten (Ki-ras)12murine sarcoma viruses, or a third member of this family (N-ras)13–15. Activation involves point mutation which often affect codon 12 (refs 16–26) of the encoded 21,000-molecular weight polypeptide (p21). To provide insight into structural requirements involved in p21 activation, we have now constructed 20 mutant c-Ha-ras1 genes byin vitromutagenesis, each encoding a different amino acid at codon 12. Analysis of rat fibroblasts transfected with these altered genes demonstrates that all amino acids except glycine (which is encoded by normal cellularrasgenes) and proline at position 12 activate p21, suggesting a requirement for anα-helical structure in this region of the polypeptide. The morphological phenotype of cells transformed by the activated genes can, however, depend on the particular amino acid at this position.