E2F1 转录因子及其对生长因子和细胞因子信号的影响。

E2F1 transcription factor and its impact on growth factor and cytokine signaling.

机构信息

Akdeniz University, Faculty of Medicine, Department of Medical Biology and Genetic, Kampus, Antalya 07070, Turkey.

出版信息

Cytokine Growth Factor Rev. 2016 Oct;31:17-25. doi: 10.1016/j.cytogfr.2016.02.001. Epub 2016 Mar 2.

DOI:10.1016/j.cytogfr.2016.02.001

Abstract

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ).

摘要

E2F1 是一种参与细胞周期调控和细胞凋亡的转录因子。E2F1 的转录激活能力受 pRb 调节。在其低磷酸化形式中，pRb 结合并使 E2F1 的 DNA 结合和转录激活功能失活。细胞的生长因子刺激导致 CDK（细胞周期蛋白依赖性激酶）的激活，反过来又磷酸化 Rb，使高磷酸化的 Rb 从 E2F1 或 E2F1/DP 复合物中释放出来，游离的 E2F1 可以诱导参与细胞周期进入、诱导或抑制细胞凋亡的几个基因的转录。因此，生长因子和细胞因子通常利用 E2F1 使细胞向任一命运分化。此外，E2F1 调节各种细胞因子和生长因子受体的表达，建立正或负反馈机制。本综述重点介绍了 E2F1 转录因子与细胞因子（IL-1、IL-2、IL-3、IL-6、TGF-β、G-CSF、LIF）、生长因子（EGF、KGF、VEGF、IGF、FGF、PDGF、HGF、NGF）和干扰素（IFN-α、IFN-β 和 IFN-γ）之间的关系。