Nagel Stefan
Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ, 38124 Braunschweig, Germany.
Biomedicines. 2021 Nov 12;9(11):1676. doi: 10.3390/biomedicines9111676.
Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in classes and subclasses, including NKL homeobox genes. In accordance with their normal functions, deregulated homeobox genes contribute to carcinogenesis along with hematopoietic malignancies. We have recently described the physiological expression of eleven NKL homeobox genes in the course of hematopoiesis and termed this gene expression pattern NKL-code. Due to the developmental impact of NKL homeobox genes these data suggest a key role for their activity in the normal regulation of hematopoietic cell differentiation including T-cells. On the other hand, aberrant overexpression of NKL-code members or ectopical activation of non-code members has been frequently reported in lymphoid and myeloid leukemia/lymphoma, demonstrating their oncogenic impact in the hematopoietic compartment. Here, we provide an overview of the NKL-code in normal hematopoiesis and discuss the oncogenic role of deregulated NKL homeobox genes in T-cell malignancies.
同源框基因编码控制基本发育过程的转录因子。同源结构域由同源框编码，介导序列特异性DNA结合以及与辅因子的相互作用，从而作为一个基本的调控平台发挥作用。它们同源框序列的相似性有助于将这些基因分类为不同的类别和亚类，包括NKL同源框基因。与它们的正常功能一致，失调的同源框基因与造血系统恶性肿瘤一起促成肿瘤发生。我们最近描述了11个NKL同源框基因在造血过程中的生理表达，并将这种基因表达模式称为NKL编码。由于NKL同源框基因对发育的影响，这些数据表明它们的活性在包括T细胞在内的造血细胞分化的正常调控中起关键作用。另一方面，NKL编码成员的异常过表达或非编码成员的异位激活在淋巴样和髓样白血病/淋巴瘤中经常被报道，这表明它们在造血系统中具有致癌作用。在此，我们概述了正常造血过程中的NKL编码，并讨论了失调的NKL同源框基因在T细胞恶性肿瘤中的致癌作用。
