Emerging links between E2F control and mitochondrial function.
Emerging links between E2F control and mitochondrial function.
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DOI：
10.1158/0008-5472.can-14-2173
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发表时间：
2015-02-15
期刊：
影响因子：
11.2
通讯作者：
Frolov MV
中科院分区：
文献类型：
--
作者：
Benevolenskaya EV;Frolov MV
E2F 转录因子家族是视网膜母细胞瘤肿瘤抑制蛋白 (pRB) 的关键下游靶标，该蛋白在人类癌症中经常失活。 E2F 因其在细胞周期调节和触发细胞凋亡中的作用而闻名。然而，E2F 与数千个基因结合，因此可以直接影响许多生物过程。鉴于潜在的 E2F 靶点过多，该领域的主要挑战是确定 E2F 发挥功能作用的特定过程以及 E2F 靶点的特定子集决定生物学结果的背景。最近的研究表明 E2F 参与线粒体相关基因表达的调节。这种调节的丧失会导致严重的线粒体缺陷。在辐射诱导的细胞凋亡过程中，其后果变得明显，其中尽管诱导了典型的凋亡基因，但 E2F 缺陷的细胞对细胞死亡不敏感。因此，E2F 的这种新功能可能对细胞活力产生重大影响，并且它独立于凋亡基因的诱导。在这里，我们讨论这些发现对癌症生物学的影响。
The family of E2F transcription factors is the key downstream target of the Retinoblastoma tumor suppressor protein (pRB), which is frequently inactivated in human cancer. E2F is best known for its role in cell cycle regulation and triggering apoptosis. However, E2F binds to thousands of genes and, thus, could directly influence a number of biological processes. Given the plethora of potential E2F targets, the major challenge in the field is to identify specific processes in which E2F plays a functional role and the contexts in which a particular subset of E2F targets dictates a biological outcome. Recent studies implicated E2F in regulation of expression of mitochondria-associated genes. The loss of such regulation results in severe mitochondrial defects. The consequences become evident during irradiation-induced apoptosis, where E2F-deficient cells are insensitive to cell death despite induction of canonical apoptotic genes. Thus, this novel function of E2F may have a major impact on cell viability, and it is independent of induction of apoptotic genes. Here, we discuss the implications of these findings in cancer biology.