Gery Sigal, Gombart Adrian F, Fung Yuen K, Koeffler H Phillip
Cedars-Sinai Medical Center, Davis Bldg 5066, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
Blood. 2004 Feb 1;103(3):828-35. doi: 10.1182/blood-2003-01-0159. Epub 2003 Aug 28.
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 myeloid 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 myeloid 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.
CCAAT增强子结合蛋白ε（C/EBPε）是一种髓系特异性转录因子，对粒细胞终末分化至关重要。视网膜母细胞瘤（Rb）和E2F1是关键的细胞周期调节因子，也与多种分化系统有关。在此，我们证明在NB4和U937人髓系细胞以及32Dcl3鼠髓系前体细胞的粒细胞分化过程中，C/EBPε与Rb和E2F1相互作用。在报告基因检测和内源性实验中，C/EBPε与Rb之间的相互作用均增强了C/EBPε介导的髓系特异性基因转录。C/EBPε-E2F1相互作用导致E2F1介导的转录活性受到抑制。最后，在人髓系细胞中过表达C/EBPε会导致c-Myc下调。我们提出，组织特异性转录因子C/EBPε与广谱蛋白Rb和E2F1之间的相互作用在C/EBPε诱导的粒细胞终末分化中起重要作用。
