C/EBPε interacts with retinoblastoma and E2F1 during granulopoiesis
C/EBPε interacts with retinoblastoma and E2F1 during granulopoiesis
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DOI：
10.1182/blood-2003-01-0159
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发表时间：
2004-02-01
期刊：
影响因子：
20.3
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
--
作者：
Gery, S;Gombart, AF;Koeffler, HP
CCAAT增强子结合蛋白epsilon(C/EBPepsilon)是一种髓系特异性转录因子，对粒细胞终末分化起重要作用。视网膜母细胞瘤(RB)和E2F1是重要的细胞周期调节因子，也参与了多种分化系统。在这里，我们证明了C/EBPepsilon在NB4和U937人髓系细胞以及32Dcl3小鼠髓系前体细胞的粒细胞分化过程中与Rb和E2F1相互作用。在报告实验和内源性实验中，C/EBPepsilon和Rb之间的相互作用增强了C/EBPepsilon介导的髓系特异性基因的转录。C/EBPepsilon-E2F1相互作用导致抑制E2F1介导的转录活性。最后，C/EBPepsilon在人骨髓细胞中的过表达导致c-Myc的下调。我们认为，组织特异性转录因子C/EBPepsilon与广谱蛋白Rb和E2F1之间的相互作用在C/EBPepsilon诱导的粒细胞终末分化中起重要作用。(C)2004年，由美国血液病学会提供。
CCAAT enhancer binding protein epsilon (C/EBPepsilon) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation. Retinoblastoma (Rb) and E2F1 are critical cell cycle regulators that also have been implicated in several differentiation systems. Here, we demonstrate that C/EBPepsilon interacts with Rb and E2F1 during granulocytic differentiation in NB4 and U937 human myeloid cells and in 32Dcl3 murine myeloid precursor cells. The interaction between C/EBPepsilon and Rb enhances C/EBPepsilon-mediated transcription of myelold specific genes both in reporter assays and endogenously. The C/EBPepsilon-E2F1 interaction results in repression of E2F1-mediated transcriptional activity. Finally, overexpression of C/EBPepsilon in human myelold cells leads to down-regulation of c-Myc. We propose that the interactions between C/EBPepsilon, a tissue-specific transcription factor, and the broad-spectrum proteins, Rb and E2F1, are important in C/EBPepsilon-induced terminal granulocytic differentiation. (C) 2004 by The American Society of Hematology.