不同e2f介导的细胞增殖、内复制和凋亡的转录机制

H. Komori, R. Iwanaga, A. Bradford, Keigo Araki, K. Ohtani
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引用次数: 0

摘要

E2F和DP家族蛋白是高等真核生物中进化保守的转录因子。E2F和DP蛋白通常形成异二聚体复合物,通过调节生长相关基因的表达来控制细胞增殖。此外,E2F家族蛋白在各种需要表达情境特异性基因的细胞事件中发挥作用。E2F蛋白在不同的环境下使用不同的机制来调节特定环境的基因。本章的主要目的是比较哺乳动物e2f介导的控制细胞增殖、内复制和凋亡的三种不同的转录调节机制。简而言之,E2F7和E2F8通过抑制其靶基因的表达来控制内复制。他们不需要DP或pRb。在细胞凋亡的控制中,E2F1通过与Arf启动子内的非规范E2F结合位点结合,以不依赖dp的方式调节肿瘤抑制基因Arf的表达。此外,我们研究了E2F和DP在果蝇中的功能,以确定那些进化上保守的E2F介导的转录调节机制。E2F蛋白如何调控上下文特异性靶基因表达的详细机制将有助于理解单个转录因子家族如何调节生物体中多种多效性细胞过程。
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Distinct E2F-Mediated Transcriptional Mechanisms in Cell Proliferation, Endoreplication and Apoptosis
E2F and DP family proteins are evolutionally conserved transcription factors among higher eukaryotes. E2F and DP proteins typically form a heterodimeric complex, which controls cell proliferation by regulating expression of growth-related genes. In addition, E2F family proteins have roles in various cellular events that require the expression of context-specific genes. E2F proteins use distinct mechanisms to regulate context-specific genes in different circumstances. The primary goal of this chapter is to compare three distinct mechanisms of mammalian E2F-mediated transcriptional regulation that control cell proliferation, endoreplication and apoptosis. Briefly, E2F7 and E2F8 control endoreplication by suppressing the expression of their target genes. They do not require DP or pRb. In control of apoptosis, E2F1 regulates the expression of the tumor suppressor gene Arf by binding to a non-canonical E2F binding site, within the Arf promoter, in a DP-independent manner. Furthermore, we examine the functions of E2F and DP in Drosophila melanogaster (fruit fly) to identify those mechanisms of E2F-mediated transcriptional regulation that have been evolutionarily conserved. The detailed mechanisms of how E2F protein regulates the expression of context-specific target genes will be instrumental in understanding how a single family of transcription factor regulates diverse pleiotropic cellular processes in an organism.
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