核内转录因子IKAROS与血液肿瘤

发布时间：2018-10-16 10:50

【摘要】：IKAROS蛋白是一类含锌指结构域的核内转录因子,调节血液细胞分化发育。机体在血液细胞分化发育、天然免疫细胞的分化成熟、抗血液系统肿瘤发生等过程中均需要IKAROS蛋白的参与。IKAROS蛋白的功能依赖于其分子结构上的2个重要结构域:DNA结合结构域和家族蛋白相互作用结构域。DNA结合结构域与靶基因上游调控序列进行特异性结合,而蛋白相互作用结构域与家族蛋白分子结合形成二聚体,发挥IKAROS的生物学活性。IKAROS蛋白在细胞内代谢受到酪蛋白激酶2(casein kinase 2,CK2)和蛋白磷酸化酶1(protein phosphorylase 1,PP1)的调节,CK2将IKAROS蛋白磷酸化,使其失去生物活性;而PP1将磷酸化的IKAROS蛋白去磷酸化,从而增强IKAROS的生物活性。近几年临床研究发现,IKAROS蛋白的表达异常以及CK2激酶活性的增高与白血病的发生发展有密切关系。本文就IKAROS的分子结构特点、生物学功能、体内代谢调控方式及IKAROS在血液系统肿瘤发生发展过程中的生物学作用进行综述。
[Abstract]:IKAROS protein is a kind of intracellular transcription factor containing zinc finger domain, which regulates the differentiation and development of blood cells. The body differentiates and develops in the blood cells, and the innate immune cells are differentiated and matured. The function of IKAROS protein depends on two important domains in its molecular structure: DNA binding domain and family protein interaction domain, DNA binding domain and DNA binding domain. The upstream regulatory sequence of the target gene is specifically bound to the target gene. The protein interaction domain binds with the family protein molecules to form dimer, which plays the biological role of IKAROS. The intracellular metabolism of IKAROS protein is regulated by casein kinase 2 (CK2) and protein phosphorylase 1 (PP1). CK2 phosphorylates IKAROS protein. PP1 dephosphorylated the phosphorylated IKAROS protein, thus enhancing the bioactivity of IKAROS. In recent years, clinical studies have found that abnormal expression of IKAROS protein and increased activity of CK2 kinase are closely related to the occurrence and development of leukemia. In this paper, the molecular structure, biological function, metabolic regulation mode of IKAROS and the biological role of IKAROS in the tumorigenesis and development of blood system are reviewed.
【作者单位】：新乡医学院基础医学院;
【基金】：国家自然科学基金(No.81602132) 新乡医学院博士科研启动基金(No.XYBSKYZZ201512&201513,No.505079)资助~~
【分类号】：R733

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