EXPRESSION OF TRANSCRIPTION FACTOR E2F1 INDUCES QUIESCENT CELLS TO ENTER S-PHASE
EXPRESSION OF TRANSCRIPTION FACTOR E2F1 INDUCES QUIESCENT CELLS TO ENTER S-PHASE
复制标题
DOI：
10.1038/365349a0
复制
发表时间：
1993-09-23
期刊：
影响因子：
64.8
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
--
作者：
JOHNSON, DG;SCHWARZ, JK;NEVINS, JR
几条证据表明E2 F转录因子是细胞增殖控制的重要组成部分。首先，在对增殖信号有反应的基因的启动子中发现E2 F结合位点，并且当这些基因中的许多被激活时，E2 F结合活性的水平增加1 -3。第二，肿瘤抑制蛋白Rb以及相关的p107蛋白与E2 F2 -7复合，导致E2 F转录活性的抑制3，8-12。第三，DNA肿瘤病毒的致癌产物可以解离这些E2 F复合物4，13。我们在此提供了E2 F参与细胞增殖控制的直接证据。具体而言，我们证明E2 F1互补DNA的过表达14，15可以激活细胞中的DNA合成，否则将生长停滞，其效率与腺病毒E1 A基因表达所实现的效率相似。此外，将E2 F1 cDNA显微注射到静止细胞中可以诱导S期进入，而两个不能反式激活DHFR和TK启动子的E2 F1突变体不能诱导S期。我们的结论是E2 F转录因子在进入S期的进展中起着重要的作用，这可能与其刺激转录的能力相一致。
SEVERAL lines of evidence implicate the E2F transcription factor as an important component of cell proliferation control. First, E2F binding sites are found in the promoters of genes responsive to proliferation signals and the level of E2F binding activity increases at a time when many of these genes are activated1-3. Second, the tumour suppressor protein Rb, as well as the related p107 protein, complexes with E2F2-7, resulting in an inhibition of E2F transcriptional activity3,8-12. Third, oncogenic products of the DNA tumour viruses can dissociate these E2F complexes4,13. We provide here direct evidence that E2F is involved in cellular proliferation control. Specifically, we demonstrate that overexpression of the E2F1 complementary DNA14,15 can activate DNA synthesis in cells that would otherwise growth-arrest, with an efficiency that is similar to that achieved by the expression of the adenovirus E1A gene. Moreover, microinjection of the E2F1 cDNA into quiescent cells can induce S-phase entry, whereas two E2F1 mutants, which are unable to transactivate the DHFR and TK promoters, are unable to induce S phase. We conclude that the E2F transcription factor plays an important role in progression into S phase and that this probably coincides with its capacity to stimulate transcription.