核内转录因子IKAROS与血液肿瘤

Nuclear Transcription Factor IKAROS and Hematologic Tumor

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。

IKAROS protein is an important nuclear transcriptional regulator with zinc finger domain, which is related to the development and differentiation of blood cells, the differentiation and maturation of natural immune cells and the involvement of malignancies in hematological system. The function of IKAROS protein depends on the two important domains, DNA binding domain and family proteins interaction domain. Wherein the DNA binding domain is used for specific binding to the upstream regulatory sequence of the target gene and the protein interaction domain is used to form a dimerization with the family protein molecule, further to exert the biological activity of IKAROS. The metabolism of IKAROS protein is regulated by casein kinase 2 （CK2） and protein phosphorylase 1 （PP1）, which CK2 can promote the IKAROS protein phosphorylation and then decrease the biological activity. While PP1 can restore the IKAROS activity via dephosphorylation, thereby enhancing the biological effect of IKAROS. In recent years, it has been found that the abnormal expression of IKAROS protein is closely related to the development of leukemia based on clinical studies. In this review, we summarized the molecular structure, biological function, metabolic regulation of IKAROS, and the influence of IKAROS in the development and progression of hematologic malignancies.