Rohwer F, Todd S, McGuire K L
Department of Biology, Molecular Biology Institute, San Diego State University, CA 92182, USA.
J Immunol. 1996 Jul 15;157(2):643-9.
IL-2 is the major mitogenic cytokine for mature human T cells. This growth factor has been shown previously to induce the expression of a number of genes, including structural proteins, proto-oncogenes, and metabolic enzymes. Multiple mechanisms, including increases in mRNA stability, protein synthesis, and new transcriptional initiation, have been studied to determine how IL-2 induces such a wide variety of genes. The following studies show that a release of transcriptional attenuation is important in IL-2-induced gene expression. A thymic blast cell system was developed and used to demonstrate that IL-2-deprived cells have a marked attenuation of transcription in the 3' ends of the pim-1 and c-myb genes. IL-2 stimulation removes this attenuation and leads to read-through transcription. This effect is gene-specific, as demonstrated by the fact that GAPDH is not attenuated in unstimulated cells. The IL-2-mediated relief of attenuation occurs within 1 h of IL-2 stimulation and is insensitive to the translation inhibitor cycloheximide, suggesting that new protein synthesis is not necessary. Further, the effect is insensitive to the immunosuppressant cyclosporin A, but is sensitive to rapamycin and the tyrosine kinase inhibitor genistein. These studies demonstrate that release of transcription attenuation is a mechanism used to induce gene expression in response to IL-2 treatment.
白细胞介素-2（IL-2）是成熟人类T细胞的主要促有丝分裂细胞因子。此前已表明，这种生长因子可诱导多种基因的表达，包括结构蛋白、原癌基因和代谢酶。人们研究了多种机制，包括mRNA稳定性增加、蛋白质合成和新的转录起始，以确定IL-2如何诱导如此多种基因。以下研究表明，转录衰减的解除在IL-2诱导的基因表达中很重要。开发了一种胸腺母细胞系统，用于证明缺乏IL-2的细胞在pim-1和c-myb基因的3'端具有明显的转录衰减。IL-2刺激消除了这种衰减并导致通读转录。这一效应具有基因特异性，如甘油醛-3-磷酸脱氢酶（GAPDH）在未刺激细胞中未出现衰减这一事实所示。IL-2介导的衰减解除在IL-2刺激后1小时内发生，且对翻译抑制剂环己酰亚胺不敏感，这表明不需要新的蛋白质合成。此外，该效应对免疫抑制剂环孢素A不敏感，但对雷帕霉素和酪氨酸激酶抑制剂染料木黄酮敏感。这些研究表明，转录衰减的解除是一种用于响应IL-2处理诱导基因表达的机制。
