Leone G, Nuckolls F, Ishida S, Adams M, Sears R, Jakoi L, Miron A, Nevins J R
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Cell Biol. 2000 May;20(10):3626-32. doi: 10.1128/MCB.20.10.3626-3632.2000.
The tumor suppressor function of Rb is intimately related to its ability to interact with E2F and repress the transcription of E2F target genes. Here we describe a novel E2F product that specifically interacts with Rb in quiescent cells. This novel E2F, which we term E2F3b, is encoded by a unique mRNA transcribed from an intronic promoter within the E2F3 locus. The E2F3b RNA differs from the previously characterized E2F3 RNA, which we now term E2F3a, by the utilization of a unique coding exon. In contrast to the E2F3a product that is tightly regulated by cell growth, the E2F3b product is expressed equivalently in quiescent and proliferating cells. But, unlike the E2F4 and E2F5 proteins, which are also expressed in quiescent cells and form complexes with the p130 protein, the E2F3b protein associates with Rb and represents the predominant E2F-Rb complex in quiescent cells. Thus, the previously described specificity of Rb function as a transcriptional repressor in quiescent cells coincides with the association of Rb with this novel E2F product.
Rb的肿瘤抑制功能与其与E2F相互作用并抑制E2F靶基因转录的能力密切相关。在此,我们描述了一种新型E2F产物,它在静止细胞中与Rb特异性相互作用。这种新型E2F,我们称之为E2F3b,由从E2F3基因座内的内含子启动子转录的独特mRNA编码。E2F3b RNA与我们现在称为E2F3a的先前表征的E2F3 RNA不同,它利用了一个独特的编码外显子。与受细胞生长严格调控的E2F3a产物相反,E2F3b产物在静止细胞和增殖细胞中表达水平相当。但是,与同样在静止细胞中表达并与p130蛋白形成复合物的E2F4和E2F5蛋白不同,E2F3b蛋白与Rb结合,是静止细胞中主要的E2F-Rb复合物。因此,先前描述的Rb在静止细胞中作为转录抑制因子的功能特异性与Rb与这种新型E2F产物的结合相一致。