tsg101: A novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells
tsg101: A novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells
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DOI：
10.1016/s0092-8674(00)81111-3
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发表时间：
1996-05-03
期刊：
影响因子：
64.5
通讯作者：
Cohen, SN
中科院分区：
文献类型：
--
作者：
Li, LM;Cohen, SN
使用一种新的策略，能够分离以前未知的编码可选择的隐性表型的基因，我们发现了一个基因(Tsg101)，它的纯合子功能中断会导致细胞转化。将来自反式激活启动子的反义RNA随机导入小鼠3T3成纤维细胞基因组中的转录基因，以敲除邻近启动子插入的染色体基因的等位基因，产生在0.5%琼脂中生长的克隆，并在裸鼠体内形成转移瘤。移除反式激活剂可以恢复正常生长。Tsg101编码的蛋白质编码一个卷曲的结构域，该结构域与Stathmin相互作用，Stathmin是一种胞质磷酸蛋白，以前与肿瘤的发生有关。在naive 3T3细胞中过表达tsg101反义转录子可导致细胞转化，并增加stathmin特异性的mRNA。
Using a novel strategy that enables the isolation of previously unknown genes encoding selectable recessive phenotypes, we identified a gene (tsg101) whose homozygous functional disruption produces cell transformation. Antisense RNA from a transactivated promoter introduced randomly into transcribed genes throughout the genome of mouse 3T3 fibroblasts was used to knock out alleles of chromosomal genes adjacent to promoter inserts, generating clones that grew in 0.5% agar and formed metastatic tumors in nude mice. Removal of the transactivator restored normal growth. The protein encoded by tsg101 cDNA encodes a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated previously in tumorigenesis. Overexpression of tsg101 antisense transcripts in naive 3T3 cells resulted in cell transformation and increased stathmin-specific mRNA.