A GENETIC-ANALYSIS OF THE E2F1-GENE DISTINGUISHES REGULATION BY RB, P107, AND ADENOVIRUS-E4
A GENETIC-ANALYSIS OF THE E2F1-GENE DISTINGUISHES REGULATION BY RB, P107, AND ADENOVIRUS-E4
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DOI：
10.1128/mcb.13.10.6314
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发表时间：
1993-10-01
影响因子：
5.3
通讯作者：
NEVINS, JR
中科院分区：
文献类型：
--
作者：
CRESS, WD;JOHNSON, DG;NEVINS, JR
细胞转录因子E2F似乎是视网膜母细胞瘤肿瘤抑制基因产物的调节作用的靶点。最近分离的E2F1 cDNA克隆，它编码的多肽特性的E2F，现在已经允许更详细的分析E2F功能的调节Rb以及Rb相关的p107蛋白和腺病毒19 kDa E4基因产物。先前的实验已经表明，这些调节蛋白中的每一个都可以调节细胞E2F的活性。我们发现，这些调控事件中的每一个都可以通过E2F1产物介导。此外，各种E2F1突变的检查揭示了这些调节蛋白的不同特异性。例如，E4改变E2F1功能的能力取决于E2F1的假定亮氨酸重复序列内以及C-末端酸性结构域内的序列。相反，亮氨酸重复元件是不重要的Rb或p107介导的抑制E2F1活性。虽然C-末端的酸性结构域的E2F1，以前被证明是重要的Rb结合，似乎是一个网站的Rb和p107的E2F1的调节，在这个区域内的点突变区分识别Rb和p107。这些结果强调了E2F调控相互作用的复杂性，也表明了Rb和p107与E2F1相互作用的定性区别，这可能反映了功能差异。
The cellular transcription factor E2F appears to be a target for the regulatory action of the retinoblastoma tumor suppressor gene product. The recent isolation of the E2F1 cDNA clone, which encodes a polypeptide with properties characteristic of E2F, has now allowed a more detailed analysis of the regulation of E2F function by Rb as well as the Rb-related p107 protein and the adenovirus 19-kDa E4 gene product. Previous experiments have shown that each of these regulatory proteins can modulate the activity of cellular E2F. We find that each of these regulatory events can be mediated through the E2F1 product. Moreover, an examination of various E2F1 mutations reveals distinct specificities for these regulatory proteins. For instance, the ability of E4 to alter E2F1 function is dependent upon sequences within a putative leucine repeat of E2F1 as well as within the C-terminal acidic domain. In contrast, the leucine repeat element was not important for Rb- or p107-mediated inhibition of E2F1 activity. Although the C-terminal acidic domain of E2F1, previously shown to be important for Rb binding, appears to be a site for regulation of E2F1 by Rb and p107, point mutations within this region distinguish recognition by Rb and p107. These results underscore the complexity of E2F regulatory interactions and also demonstrate a qualitative distinction in the interactions of Rb and p107 with E2F1, perhaps reflective of functional differences.