Sakamoto K M, Nimer S D, Rosenblatt J D, Gasson J C
Department of Pediatrics, UCLA School of Medicine.
Oncogene. 1992 Nov;7(11):2125-30.
The immediate-early response gene, EGR-1, encodes a zinc finger-containing transcription factor that is involved in growth and differentiation of a variety of cell types. EGR-1 is induced in normal T cells following mitogenic stimulation and has recently been shown to be constitutively expressed in human T-cell leukemia virus type I (HTLV-I)- and type II (HTLV-II)-transformed T-cell lines. The trans-activating protein of HTLV-I, Tax, has been demonstrated to trans-activate promoters of a number of cellular genes, some of which may be critical in regulating T-cell proliferation. In this study, we examine the effect of Tax on expression of EGR-1 in three T-cell lines and demonstrate that both HTLV-I and -II Tax are capable of trans-activating human EGR-1 recombinant promoter constructs. Interestingly, HTLV-I and -II Tax trans-activate the human EGR-1 promoter through different promoter regions in the Jurkat cell line, suggesting that HTLV-I and -II Tax may lead to constitutive expression of EGR-1 through different signaling pathways. Deregulated expression of EGR-1 may contribute to uncontrolled cell growth and transformation during early stages of T-cell activation in HTLV-I and -II-infected cells.
即刻早期反应基因EGR-1编码一种含锌指结构的转录因子,它参与多种细胞类型的生长和分化。EGR-1在有丝分裂原刺激后的正常T细胞中被诱导表达,最近研究表明它在人I型(HTLV-I)和II型(HTLV-II)人T细胞白血病病毒转化的T细胞系中组成性表达。HTLV-I的反式激活蛋白Tax已被证明可反式激活许多细胞基因的启动子,其中一些基因可能在调节T细胞增殖中起关键作用。在本研究中,我们检测了Tax对三种T细胞系中EGR-1表达的影响,并证明HTLV-I和II型Tax均能够反式激活人EGR-1重组启动子构建体。有趣的是,HTLV-I和II型Tax通过Jurkat细胞系中的不同启动子区域反式激活人EGR-1启动子,这表明HTLV-I和II型Tax可能通过不同的信号通路导致EGR-1的组成性表达。EGR-1的失调表达可能在HTLV-I和II感染细胞的T细胞激活早期阶段促成细胞的失控生长和转化。