Identification and order of sequential mutations in beta-actin genes isolated from increasingly tumorigenic human fibroblast strains.
Identification and order of sequential mutations in beta-actin genes isolated from increasingly tumorigenic human fibroblast strains.
复制标题
从致瘤性日益增强的人成纤维细胞菌株中分离出的β-肌动蛋白基因的连续突变的鉴定和排序。
DOI：
10.1073/pnas.82.20.6995
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发表时间：
1985
影响因子：
11.1
通讯作者：
Leavitt,J
中科院分区：
文献类型：
--
作者：
Lin,CS;Ng,SY;Gunning,P;Kedes,L;Leavitt,J
我们对致瘤性人成纤维细胞系（HuT-14 T）的突变型β-肌动蛋白基因进行了测序，发现它携带三个突变，改变了36、83和244位的氨基酸，以及5'内含子中的22个碱基对的“插入”序列，而野生型基因中不存在。致瘤性较低的细胞系HuT-14是HuT-14 T的祖先，具有相同的密码子-244突变和插入序列，但不具有其他两个突变。与HuT-14相关但没有β-肌动蛋白突变的非致瘤细胞系确实携带内含子长度多态性。我们得出结论，在密码子244处的突变首先发生在已经具有22个碱基对内含子插入的β-肌动蛋白等位基因中，并且在HuT-14 T表型的选择期间随后在密码子36和83处发生突变。当用单突变或三突变的β-肌动蛋白基因转染时，Rat-2细胞合成适当的电荷变体种类的突变肌动蛋白。
We have sequenced the mutant beta-actin gene of a tumorigenic human fibroblast cell line (HuT-14T) and found that it carries three mutations that alter the amino acids at positions 36, 83, and 244 as well as a 22-base-pair "insertion" sequence, in the 5' intron, not present in a wild-type gene. The less tumorigenic cell line HuT-14, a progenitor of HuT-14T, has the same codon-244 mutation and the insertion sequence but not the other two mutations. A nontumorigenic cell line that is related to HuT-14 but that has no beta-actin mutations does carry the intron-length polymorphism. We conclude that the mutation at codon 244 occurred first in a beta-actin allele already bearing the 22-base-pair intron insert and that mutations at codons 36 and 83 arose subsequently during the selection for the HuT-14T phenotype. Rat-2 cells synthesize the appropriate charge-variant species of mutant actin protein when transfected with either the singly or the triply mutated beta-actin gene.