Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo
Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo
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DOI：
10.1016/s1535-6108(02)00155-1
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发表时间：
2002-10-01
期刊：
影响因子：
50.3
通讯作者：
Look, AT
中科院分区：
文献类型：
--
作者：
Inoue, A;Seidel, MG;Look, AT
我们在这里表明，锌指转录抑制因子，蛞蝓，这是异常上调的E2 A-HLF癌蛋白在原B细胞急性白血病，功能作为一个抗凋亡因子在正常的造血祖细胞。蛞蝓（-/-）小鼠比野生型小鼠对辐射敏感得多，死亡更早，外周血细胞计数明显减少，全身有大量的微生物群和广泛传播的细菌微生物群。在不同的造血祖细胞亚群中检测到Slug表达，但在更分化的B和T淋巴细胞中未检测到Slug表达，与野生型对照组相比，辐照Slug（-/-）小鼠中凋亡（TUNEL阳性）骨髓祖细胞显著增加。这些结果表明Slug参与了一种新的存活途径，该途径保护造血祖细胞在DNA损伤后免于凋亡。
We show here that a zinc finger transcriptional repressor, Slug, which is aberrantly upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in normal hematopoietic progenitor cells. Slug(-/-) mice were much more radiosensitive than wild-type mice, dying earlier and showing accentuated decreases in peripheral blood cell counts, as well as abundant microhemorrhages and widely disseminated bacterial microabscesses throughout the body. Slug expression was detected in diverse subsets of hematopoietic progenitors, but not in more differentiated B and T lymphoid cells, and there was a significant increase in apoptotic (TUNEL-positive) bone marrow progenitor cells in irradiated Slug(-/-) mice compared to wild-type controls. These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage.