Yamanaka R, Lekstrom-Himes J, Barlow C, Wynshaw-Boris A, Xanthopoulos K G
Clinical Gene Therapy Branch, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Med. 1998 Jan;1(1):213-21. doi: 10.3892/ijmm.1.1.213.
The coordinated expression of four different CCAAT/enhancer binding proteins (C/EBPs), C/EBPalpha, C/EBPbeta, C/EBPdelta, and C/EBPepsilon constitutes a critical component of the myeloid differentiation program. C/EBPs are modular proteins, consisting of an activation domain, DNA binding domain and leucine zipper dimerization region. Recent studies including the analysis of mice deficient in several C/EBP proteins emphasize the effects of these molecules in hematopoiesis. C/EBPalpha is a master regulator of myeloid progenitors, C/EBPbeta plays an important role in macrophage and B-cell development, C/EBPgamma is involved in B-cell development, and C/EBPdelta is upregulated during myelopoiesis. Furthermore, C/EBPepsilon is a regulator of terminal differentiation of eosinophils and functional maturation of neutrophils. The formation of alternative combinations of tissue-specific and cell-stage specific C/EBP dimers may allow differential regulation of target genes in hematopoietic cells and commitment to distinctive hematopoietic lineages.
四种不同的CCAAT/增强子结合蛋白(C/EBPs),即C/EBPα、C/EBPβ、C/EBPδ和C/EBPε的协同表达构成了髓系分化程序的关键组成部分。C/EBPs是模块化蛋白,由一个激活结构域、DNA结合结构域和亮氨酸拉链二聚化区域组成。最近的研究,包括对几种C/EBP蛋白缺陷小鼠的分析,强调了这些分子在造血过程中的作用。C/EBPα是髓系祖细胞的主要调节因子,C/EBPβ在巨噬细胞和B细胞发育中起重要作用,C/EBPγ参与B细胞发育,C/EBPδ在骨髓生成过程中上调。此外,C/EBPε是嗜酸性粒细胞终末分化和中性粒细胞功能成熟的调节因子。组织特异性和细胞阶段特异性C/EBP二聚体的替代组合的形成可能允许对造血细胞中的靶基因进行差异调节,并促使细胞向不同的造血谱系分化。