Marsilio E, Cheng S H, Schaffhausen B, Paucha E, Livingston D M
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
J Virol. 1991 Oct;65(10):5647-52. doi: 10.1128/JVI.65.10.5647-5652.1991.
Simian virus 40 large T antigen (T) can transform cultured cells, but the mechanisms by which it functions are not entirely understood. Several lines of evidence have suggested that the amino-terminal approximately 130 residues of T may be sufficient to confer the transforming capability. Oligonucleotide-directed mutagenesis was used to generate a series of deletion and substitution mutants within the amino-terminal 82 residues of T, the segment which is shared with simian virus 40 small t antigen (t). Results of stability and transformation assays of these mutants strongly suggest that the 1-to-82 region of T contains sequences which govern T transforming activity and affect in vivo stability. Instability and a defect in transforming activity could be separated from one another genetically. Thus, the 1-to-82 region appears to contain a specific region that contributes to the transforming function of the protein. This segment operates by means other than the simple binding of pRb and/or p107.
猴病毒40大T抗原（T）可转化培养细胞，但其发挥作用的机制尚未完全明确。多项证据表明，T抗原氨基末端约130个氨基酸残基可能足以赋予其转化能力。利用寡核苷酸定向诱变技术，在T抗原氨基末端82个氨基酸残基（该区域与猴病毒40小t抗原（t）相同）内产生了一系列缺失和取代突变体。这些突变体的稳定性和转化分析结果强烈表明，T抗原的1至82区域包含决定T抗原转化活性并影响其体内稳定性的序列。不稳定和转化活性缺陷在遗传上是可以分开的。因此，1至82区域似乎包含一个对该蛋白转化功能有贡献的特定区域。该片段发挥作用的方式并非简单地结合视网膜母细胞瘤蛋白（pRb）和/或p107。
