Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Stem Cells. 2013 Aug;31(8):1447-53. doi: 10.1002/stem.1443.
Understanding the factors that regulate hematopoiesis opens up the possibility of modifying these factors and their actions for clinical benefit. DEK, a non-histone nuclear phosphoprotein initially identified as a putative proto-oncogene, has recently been linked to regulate hematopoiesis. DEK has myelosuppressive activity in vitro on proliferation of human and mouse hematopoietic progenitor cells and enhancing activity on engraftment of long-term marrow repopulating mouse stem cells, has been linked in coordinate regulation with the transcription factor C/EBPα, for differentiation of myeloid cells, and apparently targets a long-term repopulating hematopoietic stem cell for leukemic transformation. This review covers the uniqueness of DEK, what is known about how it now functions as a nuclear protein and also as a secreted molecule that can act in paracrine fashion, and how it may be regulated in part by dipeptidylpeptidase 4, an enzyme known to truncate and modify a number of proteins involved in activities on hematopoietic cells. Examples are provided of possible future areas of investigation needed to better understand how DEK may be regulated and function as a regulator of hematopoiesis, information possibly translatable to other normal and diseased immature cell systems.
了解调节造血的因素为我们提供了修饰这些因素及其作用的可能性,从而带来临床获益。DEK 最初被鉴定为潜在原癌基因,是一种非组蛋白核磷酸蛋白,最近与调节造血有关。DEK 在体外对人源和鼠源造血祖细胞的增殖具有骨髓抑制活性,并且增强长期骨髓重建造血小鼠干细胞的植入活性,与转录因子 C/EBPα 协调调节,促进髓系细胞分化,显然将长期重建造血的造血干细胞作为白血病转化的靶标。这篇综述涵盖了 DEK 的独特性,关于它现在如何作为核蛋白发挥作用以及作为一种可以旁分泌方式发挥作用的分泌分子的知识,以及它如何部分受到二肽基肽酶 4 的调节,这种酶已知会截断和修饰许多参与造血细胞活动的蛋白质。提供了一些可能需要进一步研究的未来领域的例子,以更好地了解 DEK 如何作为造血调节因子发挥作用的信息,这些信息可能适用于其他正常和患病的未成熟细胞系统。