Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.
Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.
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发表时间：
1996-03
期刊：
影响因子：
8
通讯作者：
Y. Geng;E. Eaton;M. Picón;J. Roberts;A. Lundberg;A. Gifford;C. Sardet;R. Weinberg
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文献类型：
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作者：
Y. Geng;E. Eaton;M. Picón;J. Roberts;A. Lundberg;A. Gifford;C. Sardet;R. Weinberg
Cyclin E对于细胞在生长周期的G1期的推进至关重要。已知细胞周期蛋白E基因的转录是细胞周期依赖的。我们之前已经表明，细胞周期蛋白E的mRNA水平受有丝分裂原的正调控，tgf - β的负调控。许多间接证据表明E2F转录因子和视网膜母细胞瘤蛋白（pRB）共同控制细胞周期蛋白E的表达。然而，这种控制的分子基础仍不清楚。我们在此报道了cyclin E启动子的克隆，并在启动子序列中鉴定了几个假定的E2F结合位点。我们发现细胞周期对周期蛋白E转录的调控是由启动子中存在的E2F结合位点介导的。该启动子的活性可受pRB负向调控。我们的研究结果表明，在G1晚期存在一个正反馈回路，其功能是确保细胞周期蛋白E的持续表达和pRB的失活。
Cyclin E is critical for the advance of cells through the G1 phase of their growth cycle. Transcription of the cyclin E gene is known to be cell cycle-dependent. We have shown previously that mRNA levels of cyclin E are regulated positively by mitogens and negatively by TGF-beta. Much circumstantial evidence implicates both E2F transcription factors and the retinoblastoma protein (pRB) in the control of cyclin E expression. However, the molecular basis of this control has remained unclear. We report here the cloning of the cyclin E promoter and the identification of several putative E2F binding sites within the promoter sequence. We have found that cell cycle regulation of cyclin E transcription is mediated by E2F binding sites present in the promoter. The activity of this promoter can be regulated negatively by pRB. Our results suggest the operation of a positive-feedback loop in late G1 that functions to ensure continued cyclin E expression and pRB inactivation.