Zhang Y, Chellappan S P
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Oncogene. 1995 Jun 1;10(11):2085-93.
The transcription factor E2F consists of a family of proteins that bind to the sequence TTTCGCGC and regulate the expression of various cellular and viral promoters. E2F binds to DNA as homodimers or as heterodimers in association with a protein, DP1 (for dimerization partner 1). E2F-DP1 heterodimers bind more efficiently than homodimers to DNA, retinoblastoma gene product as well as the adenovirus E4 protein and DP1 can stimulate transcription from E2F sites in a synergistic fashion. Here we describe the cloning and characterization of a novel human DP gene, DP2, whose product dimerizes efficiently with E2F. Unlike DP1, there appear to be multiple transcripts for DP2 and their distribution appears to vary in different tissues and cell lines. DP2 binds to E2F as detected by in vitro reconstitution assays and an E2F-DP2 heterodimer can bind to DNA in gel-retardation assays. We believe that DP2 also plays a major role in modulating the function of E2F in cell cycle regulation and oncogenesis.
转录因子E2F由一类蛋白质组成,这些蛋白质可与序列TTTCGCGC结合,并调节各种细胞和病毒启动子的表达。E2F以同二聚体形式或与蛋白质DP1(二聚化伴侣1)结合形成异二聚体的形式与DNA结合。E2F-DP1异二聚体比同二聚体更有效地与DNA结合,视网膜母细胞瘤基因产物以及腺病毒E4蛋白和DP1可以协同方式刺激E2F位点的转录。在此,我们描述了一种新型人类DP基因DP2的克隆和特性,其产物可与E2F高效二聚化。与DP1不同,DP2似乎有多种转录本,并且它们在不同组织和细胞系中的分布似乎有所不同。通过体外重组试验检测到DP2与E2F结合,并且在凝胶阻滞试验中E2F-DP2异二聚体可与DNA结合。我们认为DP2在调节E2F在细胞周期调控和肿瘤发生中的功能方面也起主要作用。