ERYTHROLEUKEMIA INDUCTION BY FRIEND MURINE LEUKEMIA-VIRUS - INSERTIONAL ACTIVATION OF A NEW MEMBER OF THE ETS GENE FAMILY, FLI-1, CLOSELY LINKED TO C-ETS-1
ERYTHROLEUKEMIA INDUCTION BY FRIEND MURINE LEUKEMIA-VIRUS - INSERTIONAL ACTIVATION OF A NEW MEMBER OF THE ETS GENE FAMILY, FLI-1, CLOSELY LINKED TO C-ETS-1
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DOI：
10.1101/gad.5.6.908
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发表时间：
1991-06-01
影响因子：
10.5
通讯作者：
BERNSTEIN, A
中科院分区：
文献类型：
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作者：
BENDAVID, Y;GIDDENS, EB;BERNSTEIN, A
在Friend鼠白血病病毒(F-MuLV)诱导的红白血病细胞克隆中，逆转录病毒整合位点Fli-1重排的比例为75%，而Friend脾病灶形成病毒(SFFV)诱导的红白血病细胞克隆中，DNA结合蛋白Ets家族成员Spi-1/PU.1的重排比例为95%。为了确定Fli-1定义的转录结构域，我们分离了一个只在具有Fli-1重排的红白血病细胞系中高表达的cDNA克隆。该基因的蛋白质序列与Ets基因家族的另一成员Erg2非常相似。Fli-1cDNA的亲水性羧基末端与ETS家族所有成员中发现的DNA结合的ETS结构域具有显著的序列相似性。PFGE分析将Fli-1定位在小鼠9号染色体和人11q23号染色体上Ets-1原癌基因240 kb的范围内，提示Ets-1和Fli-1是通过基因重复的方式来源于共同的祖先基因。小鼠Fli-1、Spi-1和禽类v-ETS基因参与了红白血病的诱导，提示ETS基因家族成员的激活在这些多阶段恶性肿瘤的发生发展中起重要作用。
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 llq23, 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.