Athanasiou Meropi, Blair Donald G, Mavrothalassitis George
Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD 21702, USA.
Anticancer Res. 2003 May-Jun;23(3A):2143-53.
Ets-family genes have been implicated in leukemia, as well as in normal hematopoiesis. ERF is an ets-related gene that represses transcription and is regulated by MAPK phosphorylation through its effect on ERF sub-cellular localization. Using pluripotent human cell lines, we studied the effect of ERF on erythroid differentiation. K562 and HEL cells expressing ERF expressed elevated levels of the erythroid-specific markers CD71 and Glycophorin A, as well as hemoglobin and GATA1. Treatment with the Erk kinase inhibitor PD98058 further enhanced the erythroid phenotype in ERF-expressing cells and cells expressing a non-phosphorylatable ERF mutant exhibited an even more enhanced phenotype. These results are consistent with the fact that ERF function is regulated by MAPK, and suggest that the effect of the MAPK pathway in erythroid differentiation is partially mediated by ERF. The effect of ERF is similar to the one shown for ETS1 and opposite to the FLI1 function in these cells, suggesting that several ets genes may play key roles in hematopoietic differentiation.
Ets家族基因与白血病以及正常造血过程有关。ERF是一种与ets相关的基因，它能抑制转录，并通过影响ERF亚细胞定位受丝裂原活化蛋白激酶（MAPK）磷酸化调控。利用多能人类细胞系，我们研究了ERF对红系分化的影响。表达ERF的K562和HEL细胞中，红系特异性标志物CD71和血型糖蛋白A、血红蛋白以及GATA1的表达水平升高。用Erk激酶抑制剂PD98058处理可进一步增强表达ERF细胞的红系表型，而表达不可磷酸化ERF突变体的细胞表现出更强的表型。这些结果与ERF功能受MAPK调控这一事实相符，并表明MAPK途径在红系分化中的作用部分是由ERF介导的。ERF的作用与这些细胞中ETS1的作用相似，与FLI1的功能相反，这表明几个ets基因可能在造血分化中起关键作用。
