Friedman Alan D
Division of Pediatric Oncology, Johns Hopkins University, CRB I, Room 253, 1650 Orleans St., Baltimore, MD 21231, USA.
Blood Cells Mol Dis. 2007 Nov-Dec;39(3):340-3. doi: 10.1016/j.bcmd.2007.06.010. Epub 2007 Jul 31.
C/EBPalpha and PU.1 are key regulators of early myeloid development. Mice lacking C/EBPalpha or PU.1 have reduced granulocytes and monocytes. Consistent with a model in which induction of PU.1 by C/EBPalpha contributes to monocyte lineage specification, mice with reduced PU.1 have diminished monocytes but retain granulocytes, C/EBPalpha directly activates PU.1 gene transcription, and exogenous C/EBPalpha increases monocytic lineage commitment from bipotential myeloid progenitors. In addition to C/EBPalpha, AP-1 proteins also have the capacity to induce monocytic maturation. C/EBPalpha:c-Jun or C/EBPalpha:c-Fos leucine zipper heterodimers induce monopoiesis more potently than C/EBPalpha or c-Jun homodimers or c-Fos:c-Jun heterodimers. C/EBPs and NF-kappaB cooperatively regulate numerous genes during the inflammatory response. The C/EBPalpha basic region interacts with NF-kappaB p50, but not p65, to induce bcl-2, and this interaction may be relevant to myeloid cell survival and development.
C/EBPα和PU.1是早期髓系发育的关键调节因子。缺乏C/EBPα或PU.1的小鼠粒细胞和单核细胞数量减少。与C/EBPα诱导PU.1有助于单核细胞谱系特化的模型一致，PU.1减少的小鼠单核细胞减少但保留粒细胞，C/EBPα直接激活PU.1基因转录，外源性C/EBPα增加双潜能髓系祖细胞向单核细胞谱系的定向分化。除C/EBPα外，AP-1蛋白也有诱导单核细胞成熟的能力。C/EBPα:c-Jun或C/EBPα:c-Fos亮氨酸拉链异二聚体比C/EBPα或c-Jun同二聚体或c-Fos:c-Jun异二聚体更有效地诱导单核细胞生成。在炎症反应期间，C/EBPs和NF-κB协同调节众多基因。C/EBPα的碱性区域与NF-κB p50相互作用，而不与p65相互作用，以诱导bcl-2，这种相互作用可能与髓系细胞的存活和发育有关。
