E2F-1 ACCUMULATION BYPASSES A G(1) ARREST RESULTING FROM THE INHIBITION OF G(1) CYCLIN-DEPENDENT KINASE-ACTIVITY
E2F-1 ACCUMULATION BYPASSES A G(1) ARREST RESULTING FROM THE INHIBITION OF G(1) CYCLIN-DEPENDENT KINASE-ACTIVITY
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DOI：
10.1101/gad.9.23.2873
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发表时间：
1995-12-15
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：
DEGREGORI, J;LEONE, G;NEVINS, JR
许多实验定义了G（1）细胞周期蛋白和相关激酶在允许细胞正常从静态状态，通过G（1）和S相中的关键作用。现在，我们证明G（1）细胞周期蛋白依赖性激酶活性对于G（1）后期E2F活性的积累至关重要。此外，E2F-1的过表达可以克服g（1）抑制细胞周期蛋白依赖性激酶活性引起的g（1）停滞，与E2F激活一致，这是G（1）细胞周期蛋白作用的重要结果。 E2F-1还克服了由γ辐射引起的A G（1）块，并导致细胞基因组和进入有丝分裂的明显复制。 E2F-1介导的S相和有丝分裂的诱导不伴随着通常在细胞周期的G（1）期间观察到的细胞周期蛋白D相关激酶活性或CDK2活性的增加。我们得出的结论是，G（1）Cyclin依赖性激酶活性的一个关键功能是E2F-1的激活，E2F活性的积累可能足以允许启动和完成S相，但是包括G（包括G（包括G（ 1）细胞周期蛋白激酶活性对于正常增殖事件可能是必需的。
Numerous experiments have defined a critical role for the G(1) cyclins and associated kinases in allowing a normal progression of cells from a quiescent state, through G(1), and into S phase. We now demonstrate that G(1) cyclin-dependent kinase activity is critical for the accumulation of E2F activity late in G(1). Moreover, E2F-1 overexpression can overcome a G(1) arrest caused by the inhibition of G(1) cyclin-dependent kinase activity, consistent with E2F activation being an important consequence of the action of G(1) cyclins. E2F-1 also overcomes a G(1) block caused by gamma irradiation and leads to an apparent complete replication of the cellular genome and entry into mitosis. This E2F-1-mediated induction of S phase and mitosis is not accompanied by the rise in either cyclin D-associated kinase activity or cdk2 activity that is normally observed during the G(1) phase of the cell cycle. We conclude that one key function for G(1) cyclin-dependent kinase activity is the activation of E2F-1, that the accumulation of E2F activity may be sufficient to allow initiation and completion of S phase, but that additional events, including G(1) cyclin kinase activity, are likely necessary for a normal proliferative event.