ISG15 modulates development of the erythroid lineage.

ISG15 modulates development of the erythroid lineage.
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DOI:
10.1371/journal.pone.0026068
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Quang CT
Quang CT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Maragno AL;Pironin M;Alcalde H;Cong X;Knobeloch KP;Tangy F;Zhang DE;Ghysdael J;Quang CT

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促红细胞生成素受体的激活使红细胞生成。为了寻找在这一分化过程中被上调的基因,我们确定了ISG15在红系晚期分化过程中被诱导。ISG15属于泛素样蛋白家族,通过isg酰化机制的酶与靶蛋白共价连接。通过在体内和体外分化红母细胞,我们发现ISG15以及与ISGylation过程相关的酶Ube1L、UbcM8和Herc6的表达在红母细胞分化过程中被诱导。小鼠ISG15缺失导致骨髓中BFU-E/CFU-E数量减少,同时脾脏中这些细胞数量增加。ISG15-/-骨髓和脾脏来源的红母细胞在体内和体外均表现出分化程度较低的表型,并且发现ISG15在红母细胞中过表达可促进红细胞分化。此外,我们已经证明红细胞发育的重要参与者,如STAT5, Globin, PLC γ和ERK2在红细胞中被isgayated。这表明ISG15在红细胞分化过程中除了具有抗病毒功能外,还有一个新的作用。
Activation of erythropoietin receptor allows erythroblasts to generate erythrocytes. In a search for genes that are up-regulated during this differentiation process, we have identified ISG15 as being induced during late erythroid differentiation. ISG15 belongs to the ubiquitin-like protein family and is covalently linked to target proteins by the enzymes of the ISGylation machinery. Using both in vivo and in vitro differentiating erythroblasts, we show that expression of ISG15 as well as the ISGylation process related enzymes Ube1L, UbcM8 and Herc6 are induced during erythroid differentiation. Loss of ISG15 in mice results in decreased number of BFU-E/CFU-E in bone marrow, concomitant with an increased number of these cells in the spleen of these animals. ISG15-/- bone marrow and spleen-derived erythroblasts show a less differentiated phenotype both in vivo and in vitro, and over-expression of ISG15 in erythroblasts is found to facilitate erythroid differentiation. Furthermore, we have shown that important players of erythroid development, such as STAT5, Globin, PLC γ and ERK2 are ISGylated in erythroid cells. This establishes a new role for ISG15, besides its well-characterized anti-viral functions, during erythroid differentiation.
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