Taniguchi T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Annu Rev Immunol. 1988;6:439-64. doi: 10.1146/annurev.iy.06.040188.002255.
Following the isolation and characterization of many cytokine genes, we began to understand the mechanisms regulating cytokine gene expression. Needless to say, understanding the mechanisms by which induction of gene expression occurs in a transient, cell type-specific manner in response to extracellular inducers is a central issue in eukaryotic molecular biology. The cytokine systems represent suitable models for studying the mechanisms regulating gene expression, since the expression of cytokines appears to be tightly regulated by restricted types of cells and inducers. At present, cis-acting DNA sequences involved in gene regulation have been identified in only a few cytokine genes. Little is known about the nature of factors regulating the cytokine gene expression. Of particular interest are the mechanisms by which the extracellular stimulation of the cells delivers signals in the nucleus and how they turn on the otherwise nonoperative transcription machinery. In many cases, the induction of the genes will involve the activation of preexisting factors rather than the de novo protein synthesis by modifications of the factors. Dysregulation of cytokine gene expression may be caused by chromosomal alterations or by infection of viruses that induce activation or inactivation of the expression machinery. This process may be crucial in the etiology of various diseases including neoplasms. To understand the complex nature of cytokine action in the regulation of cell proliferation, differentiation, and function, more attention should also be focused on the genes encoding the respective receptors.
在分离和鉴定了许多细胞因子基因之后，我们开始了解调节细胞因子基因表达的机制。不言而喻，理解基因表达如何在细胞外诱导物的作用下以瞬时、细胞类型特异性的方式发生，是真核分子生物学的核心问题。细胞因子系统是研究调节基因表达机制的合适模型，因为细胞因子的表达似乎受到特定类型的细胞和诱导物的严格调控。目前，仅在少数细胞因子基因中鉴定出了参与基因调控的顺式作用DNA序列。对于调节细胞因子基因表达的因子的性质了解甚少。特别令人感兴趣的是细胞的细胞外刺激如何在细胞核中传递信号以及它们如何开启原本不起作用的转录机制。在许多情况下，基因的诱导将涉及预先存在的因子的激活，而不是通过因子的修饰进行从头蛋白质合成。细胞因子基因表达的失调可能由染色体改变或诱导表达机制激活或失活的病毒感染引起。这个过程在包括肿瘤在内的各种疾病的病因学中可能至关重要。为了理解细胞因子在调节细胞增殖、分化和功能中的复杂作用性质，还应更多地关注编码各自受体的基因。
