TRANSIENT REVERSION OF RAS ONCOGENE-INDUCED CELL-TRANSFORMATION BY ANTIBODIES SPECIFIC FOR AMINO-ACID 12 OF RAS PROTEIN
TRANSIENT REVERSION OF RAS ONCOGENE-INDUCED CELL-TRANSFORMATION BY ANTIBODIES SPECIFIC FOR AMINO-ACID 12 OF RAS PROTEIN
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DOI：
10.1038/314639a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
MCCORMICK, F
中科院分区：
文献类型：
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作者：
FERAMISCO, JR;CLARK, R;MCCORMICK, F
由癌基因编码的蛋白质被认为在某些类型的癌细胞中触发转化表型的表达。在人类细胞中，thras蛋白家族由几个成员组成，包括正常（原癌基因）和突变（癌基因）形式1 -3。一般来说，原癌基因形式被认为参与细胞的正常生长控制，而突变形式（显然是由正常基因的体细胞突变引起的）似乎部分地负责正常生长控制的丧失。显微注射到活的正常细胞中，纯化的癌基因蛋白（p21）在几小时内诱导细胞生长控制的特征性丧失4，5。差异蛋白的突变形式通常包含单个氨基酸变化，通常在位置12或较少在位置61（参考文献6）。在这里，我们报告说，显微注射的致癌v-Ki-ras蛋白的氨基酸12特异性的抗体到细胞转化由这种蛋白质引起的细胞瞬时逆转为正常表型。该抗体抑制GTP与v-Ki-ras蛋白结合的事实支持GTP结合对于该致癌基因产物的转化功能是必需的这一观点。
The proteins encoded by therasoncogene are thought to trigger expression of the transformed phenotype in some types of cancer cells. In human cells, therasprotein family consists of several members including normal (proto-oncogene) and mutant (oncogene) forms1–3. In general, the proto-oncogene forms are thought to be involved in the normal growth control of cells, while the mutant forms (which apparently result from somatic mutation of the normalrasgenes) appear to be responsible, in part, for the loss of normal growth control. On microinjection into living normal cells, the purifiedrasoncogene protein (p21) induces a characteristic loss of growth control in cells within several hours4,5. The mutant forms of the differentrasproteins typically contain a single amino-acid change, usually at position 12 or less frequently at position 61 (ref. 6). Here we report that microinjection of antibodies specific for amino acid 12 of the oncogenic v-Ki-rasprotein into cells transformed by this protein causes a transient reversion of the cells to a normal phenotype. The fact that this antibody inhibits binding of GTP to the v-Ki-rasprotein supports the notion that GTP binding is essential to the transforming function of this oncogene product.