AUTOREGULATORY CONTROL OF E2F1 EXPRESSION IN RESPONSE TO POSITIVE AND NEGATIVE REGULATORS OF CELL-CYCLE PROGRESSION
AUTOREGULATORY CONTROL OF E2F1 EXPRESSION IN RESPONSE TO POSITIVE AND NEGATIVE REGULATORS OF CELL-CYCLE PROGRESSION
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DOI：
10.1101/gad.8.13.1514
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发表时间：
1994-07-01
影响因子：
10.5
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
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作者：
JOHNSON, DG;OHTANI, K;NEVINS, JR
正信号和负信号都控制着细胞从G（1）期进入S期的进程，各种数据表明E2F转录因子是一类负调节因子Rb家族生长抑制因子作用的靶点。我们现在发现，E2F1基因，编码E2F活性的一个组成部分，在从G（0）到S期的进展过程中受到自身调节控制，这主要反映了G（0）和早期G（1）的负控制，此时大多数E2F活性作为与Rb家族成员的复合物存在。此外，我们发现静止细胞中G（1）细胞周期蛋白的失调表达会刺激E2 F1启动子，并且这会通过E2 F依赖性方式的细胞周期蛋白依赖性激酶的共表达而增强。我们的结论是，E2F1基因是G（1）细胞周期蛋白依赖性激酶活性的下游靶点，最有可能是Rb家族成员磷酸化的结果，E2F1转录的自动调节可能提供了一个敏感的开关，用于调节从G（1）到S期过渡期间E2F活性的积累。
Both positive and negative signals govern the progression of cells from G(1) into S phase, and a variety of data implicate the E2F transcription factor as a target for the action of one class of negative regulators, the Rb family of growth suppressors. We now find that the E2F1 gene, which encodes one of the components of E2F activity, is subject to autoregulatory control during progression from G(0) to S phase and that this primarily reflects a negative control in G(0) and early G(1), a time when the majority of E2F activity exits as a complex with Rb family members. In addition, we find that deregulated expression of G(1), cyclins in quiescent cells stimulates the E2F1 promoter and that this is augmented by coexpression of cyclin-dependent kinases in an E2F-dependent manner. We conclude that the E2F1 gene is a downstream target for G(1) cyclin dependent kinase activity, most likely as a consequence of phosphorylation of Rb family members, and that the autoregulation of E2F1 transcription may provide a sensitive switch for regulating the accumulation of E2F activity during the transition from G(1) to S phase.