Ben-David Y, Giddens E B, Letwin K, Bernstein A
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Genes Dev. 1991 Jun;5(6):908-18. doi: 10.1101/gad.5.6.908.
The retroviral integration site Fli-1 is rearranged in 75% of the erythroleukemia cell clones induced by Friend murine leukemia virus (F-MuLV), whereas Spi-1/PU.1, a member of the ets family of DNA-binding proteins, is rearranged in 95% of the erythroleukemias induced by Friend spleen focus-forming virus (SFFV). To determine the transcriptional domain defined by Fli-1, we have isolated a cDNA clone that is highly expressed only in erythroleukemia cell lines with Fli-1 rearrangements. The protein sequence of this cDNA is very similar to Erg2, another member of the ets gene family. The hydrophilic carboxy-terminal end of the Fli-1 cDNA shares significant sequence similarity to the DNA-binding ETS domain found in all members of the ets family. PFGE analysis localized Fli-1 within 240 kb of the ets-1 proto-oncogene on mouse chromosome 9 and human chromosome 11q23, suggesting that ets-1 and Fli-1 arose from a common ancestral gene by gene duplication. The involvement of the murine Fli-1, Spi-1, and avian v-ets genes in erythroleukemia induction suggests that activation of ets gene family members plays an important role in the progression of these multistage malignancies.
逆转录病毒整合位点Fli-1在由Friend小鼠白血病病毒（F-MuLV）诱导的75%的红白血病细胞克隆中发生重排，而ets家族DNA结合蛋白成员之一的Spi-1/PU.1在由Friend脾集落形成病毒（SFFV）诱导的95%的红白血病中发生重排。为了确定由Fli-1定义的转录结构域，我们分离出了一个仅在具有Fli-1重排的红白血病细胞系中高表达的cDNA克隆。该cDNA的蛋白质序列与ets基因家族的另一个成员Erg2非常相似。Fli-1 cDNA的亲水性羧基末端与ets家族所有成员中发现的DNA结合ETS结构域具有显著的序列相似性。脉冲场凝胶电泳（PFGE）分析将Fli-1定位在小鼠9号染色体和人类11q23上ets-1原癌基因的240 kb范围内，这表明ets-1和Fli-1是由一个共同的祖先基因通过基因复制产生的。小鼠Fli-1、Spi-1和禽类v-ets基因参与红白血病诱导表明，ets基因家族成员的激活在这些多阶段恶性肿瘤的进展中起重要作用。
