FUNCTIONAL ROLE OF FLI-1 IN NEOPLASIA

小鼠Fli-1基因在75%的红白血病中重排 由Friend鼠白血病病毒诱导。我们克隆并鉴定了 人类Fli-1基因我们的结果表明Fli-1基因编码 序列特异性DNA结合蛋白作为转录因子， 活化剂。Fli-1基因也被证明参与了几种人类实体瘤的形成。 携带t（11;22）染色体的肿瘤（尤因肿瘤家族） 易位我们克隆了异常EWS-Fli-1融合cDNA， 在这些人类实体瘤中。EWS-Fli-1蛋白的功能分析 揭示了它们作为序列特异性转录因子的功能， 活化剂。最近的研究表明，癌蛋白和病毒 蛋白质不仅在细胞增殖中起主要作用，而且在细胞凋亡中也起重要作用。 分化和凋亡。我们最近的研究结果表明， 异常的Fli-1蛋白抑制细胞凋亡。我们打算研究 Fli-1蛋白的DNA结合和反式激活在抑制 凋亡我们还计划研究Fli-i如何与已知的 细胞死亡途径，以获得Fli-1及其靶点的作用的线索 基因调节的生存和肿瘤性质 造血细胞

Mouse Fli-1 gene is shown to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have cloned and characterized the human Fli-1 gene. Our results demonstrate that Fli-1 gene codes for sequence specific DNA binding proteins that act as transcriptional activators. Fli-1 gene is also shown to be involved in several human solid tumors (Ewing family of tumors) carrying t(11;22) chromosome translocation. We have cloned the aberrant EWS-Fli-1 fusion cDNAs involved in these human solid tumors. Functional analysis of EWS-Fli-1 proteins revealed that they function as sequence specific transcriptional activators. Recent studies suggest that both oncoproteins and viral proteins play major role not only in cell proliferation but also in cell differentiation and apoptosis. Our recent results suggest that both normal and aberrant Fli-1 proteins inhibit apoptosis. We intend to study the role of DNA binding and transactivation of Fli-1 proteins in the inhibition of apoptosis. We also plan to study how Fli-i interacts with already known cell death pathways to get a clue for the role of Fli-1 and its target genes in modulating both survival and neoplastic properties of hematopoietic cells.