Zhang N, Shen W F, Ho A D, Lu M
Cancer Center, University of California at San Diego 92103-8421.
Cancer Res. 1995 Mar 1;55(5):1117-21.
HOX-11 (TCL-3) is a homeobox proto-oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation associated with pediatric T-cell acute leukemia. To better understand the transcriptional regulation of the HOX-11 gene in response to extracellular signals, the levels of HOX-11 RNA were examined in normal and leukemic human T cells upon phytohemagglutinin and hematopoietic growth factor stimulation. While individual hematopoietic growth factors tested did not show any effect on HOX-11 gene expression, a drastic increase in HOX-11 RNA was observed under the induction of phytohemagglutinin. In the presence of cycloheximide, a protein synthesis inhibitor, phytohemagglutinin-induced HOX-11 up-regulation was suppressed, indicating that HOX-11 acts as a delayed early response gene which requires protein synthesis. The HOX-11 gene expression was also suppressed by the tyrosine kinase inhibitors tryphostin and lavendustin A. Our data therefore suggest that the delayed early response of HOX-11 up-regulation in T cells requires a tyrosine phosphorylation signal.
HOX - 11（TCL - 3）是一种从与儿童T细胞急性白血病相关的t(10;14)染色体易位断点区域分离出的同源框原癌基因。为了更好地理解HOX - 11基因在响应细胞外信号时的转录调控，我们检测了在植物血凝素和造血生长因子刺激下，正常和白血病人类T细胞中HOX - 11 RNA的水平。虽然所检测的单个造血生长因子对HOX - 11基因表达没有任何影响，但在植物血凝素诱导下，观察到HOX - 11 RNA急剧增加。在存在蛋白质合成抑制剂环己酰亚胺的情况下，植物血凝素诱导的HOX - 11上调受到抑制，这表明HOX - 11作为一个延迟早期反应基因，其上调需要蛋白质合成。HOX - 11基因表达也受到酪氨酸激酶抑制剂曲磷胺和拉文达ustin A的抑制。因此，我们的数据表明，T细胞中HOX - 11上调的延迟早期反应需要酪氨酸磷酸化信号。
