Impaired maturation of myeloid progenitors in mice lacking novel Polycomb group protein MBT-1
Impaired maturation of myeloid progenitors in mice lacking novel Polycomb group protein MBT-1
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DOI：
10.1038/sj.emboj.7600654
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发表时间：
2005-05-18
期刊：
影响因子：
11.4
通讯作者：
Miyazaki, T
中科院分区：
文献类型：
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作者：
Arai, S;Miyazaki, T
多梳族 (PcG) 蛋白参与具有基因抑制活性的 DNA 结合复合物，其中许多蛋白因其参与造血作用而受到关注。我们已经鉴定了一种假定的 PcG 蛋白，称为 MBT-1，它与 Rnf2（PcG 蛋白的体内相互作用因子）相关。 MBT-1 在结构上类似于 H-L(3)MBT 蛋白，预计该蛋白的缺失会导致骨髓造血系统恶性肿瘤。人类 MBT-1 基因位于染色体 6q23 上，该区域在白血病细胞中经常被删除，并且在髓系白血病细胞中显示出短暂的表达高峰，以响应成熟诱导的刺激。 MBT-1(-/-) 骨髓祖细胞表现出成熟缺陷，但维持正常的增殖活性。这导致未成熟的骨髓祖细胞的积累，因此成熟的骨髓血细胞显着减少，导致MBT-1(-/-)小鼠在胚胎晚期死于贫血。总之，我们得出结论，MBT-1 在两个发育阶段之间的过渡期间特异性调节骨髓祖细胞的成熟进程。我们还表明 MBT-1 似乎通过瞬时增强 p57(KIP2) 表达水平来影响骨髓细胞生成。
Polycomb group (PcG) proteins participate in DNA-binding complexes with gene-repressing activity, many of which have been highlighted for their involvement in hematopoiesis. We have identified a putative PcG protein, termed MBT-1, that is associated with Rnf2, an in vivo interactor of PcG proteins. MBT-1 structurally resembles the H-L(3)MBT protein, whose deletion is predicted to be responsible for myeloid hematopoietic malignancies. The human MBT-1 gene is located on chromosome 6q23, a region frequently deleted in leukemia cells, and shows a transient expression spike in response to maturation-inducing stimuli in myeloid leukemia cells. MBT-1(-/-) myeloid progenitor cells exhibit a maturational deficiency but maintain normal proliferative activities. This results in the accumulation of immature myeloid progenitors and hence, a marked decrease of mature myeloid blood cells, causing the MBT-1(-/-) mice to die of anemia during a late embryonic stage. Together, we conclude that MBT-1 specifically regulates the maturational advancement of myeloid progenitor cells during transitions between two developmental stages. We also show that MBT-1 appears to influence myelopoiesis by transiently enhancing p57(KIP2) expression levels.