Reddy E S, Rao V N
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Cancer Res. 1990 Aug 15;50(16):5013-6.
The avian acute leukemia virus (E26) induces a mixed erythroid-myeloid leukemia in chickens and carries two distinct oncogenes, v-myb and v-ets. The viral protein responsible for transformation is a gag-myb-ets fusion protein that is located in the nucleus of the transformed cells. The cellular homologue of v-ets (c-ets-1) is highly expressed in lymphoid cells and differs from the v-ets gene at its carboxy terminal region. Here, we show that both the c-ets-1 and v-ets gene products are DNA-binding proteins and their DNA-binding activity is located in the carboxy terminal (46 amino acid residues) region. It appears that this DNA-binding activity is modulated by the extreme carboxy terminal region. The amino acid sequences of the putative ets DNA-binding domain at its carboxy terminal region showed a helix-turn-helix secondary structure. Exchanging the nonhomologous extreme carboxy terminal regions of c-ets-1 with v-ets gene sequences showed differences in DNA-binding affinity, indicating that these differences may be partly responsible for the activation of the ets oncogene.
禽急性白血病病毒（E26）可在鸡中诱发混合性红系-髓系白血病，并携带两个不同的癌基因，即v-myb和v-ets。负责转化的病毒蛋白是一种gag-myb-ets融合蛋白，位于转化细胞的细胞核中。v-ets的细胞同源物（c-ets-1）在淋巴细胞中高度表达，并且在其羧基末端区域与v-ets基因不同。在这里，我们表明c-ets-1和v-ets基因产物都是DNA结合蛋白，并且它们的DNA结合活性位于羧基末端（46个氨基酸残基）区域。看来这种DNA结合活性受极端羧基末端区域的调节。其羧基末端区域推定的ets DNA结合结构域的氨基酸序列显示出螺旋-转角-螺旋二级结构。将c-ets-1的非同源极端羧基末端区域与v-ets基因序列交换后，显示出DNA结合亲和力的差异，表明这些差异可能部分导致了ets癌基因的激活。
