Specificity in the activation and control of transcription factor E2F-dependent apoptosis
Specificity in the activation and control of transcription factor E2F-dependent apoptosis
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DOI：
10.1073/pnas.1831408100
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发表时间：
2003-09-16
影响因子：
11.1
通讯作者：
Nevins, JR
中科院分区：
文献类型：
--
作者：
Hallstrom, TC;Nevins, JR
先前的研究已经证明了E2F1基因产物在细胞凋亡信号传导中的作用，这既是Rb/E2F通路的失调的结果，也是对DNA损伤的反应。我们现在表明，细胞抑制E2F1凋亡潜能的能力，就像正常细胞增殖过程中可能发生的那样，需要ras -磷酸肌肽3-激酶- akt信号通路的作用。此外，我们还在E2F1蛋白中发现了一个结构域（以前称为标记框结构域），该结构域对E2F1的凋亡活性至关重要，并将E2F1蛋白与E2F3区分开来。我们还发现e2f1标记盒结构域对于诱导p53和p73的积累至关重要。重要的是，标记盒结构域在e2f1介导的细胞凋亡特异性中的作用与最近的研究一致，表明该结构域在转录激活中实现特异性的作用。我们得出结论，E2F1触发凋亡的独特能力反映了转录激活电位的特异性，并且E2F1的这种作用是通过Akt蛋白激酶的作用来调节的。
Previous work has demonstrated a role for the E2F1 gene product in signaling apoptosis, both as a result of the deregulation of the Rb/E2F pathway as well as in response to DNA damage. We now show that the ability of cells to suppress the apoptotic potential of E2F1, as might occur during the course of normal cellular proliferation, requires the action of the Ras-phosphoinositide 3-kinase-Akt signaling pathway. In addition, we also identify a domain within the E2F1 protein, previously termed the marked-box domain, that is essential for the apoptotic activity of E2F1 and that distinguishes the E2F1 protein from E2F3. We also show that the E2F1-marked-box domain is essential for the induction of both p53 and p73 accumulation. Importantly, a role for the marked-box domain in the specificity of E2F1-mediated apoptosis coincides with recent work demonstrating a role for this domain in achieving specificity in the activation of transcription. We conclude that the unique capacity of E2F1 to trigger apoposis reflects a specificity of transcriptional activation potential, and that this role for E2F1 is regulated through the action of the Akt protein kinase.