Tax oncoprotein trans-represses endogenous B-myb promoter activity in human T cells.
Tax oncoprotein trans-represses endogenous B-myb promoter activity in human T cells.
复制标题
Tax 癌蛋白反式抑制人 T 细胞中的内源 B-myb 启动子活性。
DOI：
10.1089/08892220050193065
复制
发表时间：
2000
影响因子：
1.5
通讯作者：
Franchini,G
中科院分区：
文献类型：
--
作者：
Nicot,C;Opavsky,R;Mahieux,R;Johnson,JM;Brady,JN;Wolff,L;Franchini,G
B-myb基因是根据其与原癌基因c-myb的同源性鉴定的，c-myb是禽成髓细胞瘤病毒（AMV）和禽白血病病毒（E26）转化基因的同源物。 一些使用反义构建体或反义寡核苷酸以及过表达实验的研究表明，B-Myb在G1期到S期的转变中起重要作用 B-Myb的表达受细胞周期调控。我们以前已经证明，人类T细胞嗜淋巴细胞病毒1型（HTLV 1）反式激活因子Tax能够抑制 在人T细胞中从c-myb启动子报告构建体以及从内源性c-myb启动子转录，并且这种作用是通过抑制c-myb反式激活 功能协调发展的在这里，我们报告HTLV-1和HTLV-2 Tax蛋白都抑制小鼠胚胎成纤维细胞（MEF）中的c-Myb反式激活。除c-Myb外，B-Myb表达也显著增加。 在HTLV-1转化的细胞中在RNA和蛋白质水平下调。此外，通过使用用镉诱导型启动子驱动的atax基因（JPX 9）稳定转染的Jurkat T细胞系， 我们能够证明Tax直接抑制T细胞中的内源性B-myb启动子。由于c-Myb和B-Myb参与细胞周期进程，我们的结果表明，Tax， 通过抑制c-Myb和B-Myb内源性启动子，可以绕过它们在HTLV-1转化的T细胞中对细胞周期进展的需要。
The B-mybgene was identified on the basis of its homology with the protooncogene c-myb, homolog of the avian myeloblastosis virus (AMV) and avian leukemia virus (E26) transforming genes. Several studies using antisense constructs or antisense oligonucleotides as well as overexpression experiments suggest that B-Myb plays an important role in the transition from G1to S phase of the cell cycle and that B-Myb expression is cell cycle regulated. We have previously demonstrated that the human T cell lymphotropic virus type 1 (HTLV1)trans-activator Tax is able to repress transcription from c-mybpromoter reporter constructs as well as from the endogenous c-mybpromoter in human T cells and that this effect is mediated through inhibition of the c-Mybtrans-activating functions. Here we report that both HTLV-1 as well as HTLV-2 Tax proteins inhibit c-Mybtrans-activation in mouse embryo fibroblasts (MEFs). In addition to c-Myb, B-Myb expression is also markedly downregulated in HTLV-1-transformed cells at both RNA and protein levels. Furthermore, by using a Jurkat T cell line stably transfected with ataxgene driven by a cadmium-inducible promoter (JPX9), we were able to demonstrate that Tax directly represses the endogenous B-mybpromoter in T cells. Because c-Myb and B-Myb have been involved in cell cycle progression, our results suggest that Tax, by repressing both c-Myb and B-Myb endogenous promoters, may bypass their requirement for cell cycle progression in HTLV-1-transformed T cells.