Moran E
Cold Spring Harbor Laboratory, New York 11724.
Nature. 1988 Jul 14;334(6178):168-70. doi: 10.1038/334168a0.
SV40 large T antigen contains a small region of amino acid sequence, conserved among the papovaviruses, that shows considerable similarity to conserved domain 2 of the adenovirus E1A oncogene, a domain which plays an important role in the E1A transforming functions. To learn whether the analogous SV40 T antigen sequences could substitute functionally for E1A domain 2, a chimaeric gene was constructed, coding for T antigen amino acid residues 101 to 118 in place of E1A domain 2. The resulting product showed much of the activity of the wild-type E1A products. It induced proliferation of primary BRK cells and cooperated with the ras oncogene to transform these cells fully. In addition, the chimaeric protein coprecipitated two cellular proteins whose specific binding to the E1A products depends on the presence of domain 2. The activity of the chimaeric product suggests that a similar functional unit exists in the transforming proteins of both SV40 and adenovirus, and that these proteins may exert their cell growth regulating effects through similar mechanisms.
SV40大T抗原含有一小段氨基酸序列，在乳头瘤多瘤空泡病毒中保守，该序列与腺病毒E1A癌基因的保守结构域2有相当大的相似性，E1A癌基因的这一结构域在其转化功能中起重要作用。为了了解SV40 T抗原的类似序列是否能在功能上替代E1A结构域2，构建了一个嵌合基因，编码T抗原的第101至118位氨基酸残基以取代E1A结构域2。所得产物表现出许多野生型E1A产物的活性。它诱导原代BRK细胞增殖，并与ras癌基因协同作用，使这些细胞完全转化。此外，嵌合蛋白共沉淀了两种细胞蛋白，它们与E1A产物的特异性结合取决于结构域2的存在。嵌合产物的活性表明，SV40和腺病毒的转化蛋白中存在类似的功能单元，并且这些蛋白可能通过类似的机制发挥其细胞生长调节作用。
