AktFoxO传导通路调节细胞凋亡作用的研究进展.pdfVIP

中华老年多器官疾病杂志 2013 年12 月28 日第 12 卷 第 12 期 Chin J Mult Organ Dis Elderly, Vol.12, No.12, Dec 28, 2013 ·949 · ·综 述 · Akt/FoxO传导通路调节细胞凋亡作用的研究进展 姚 越，孟 佳，姜礼红，张一娜* （哈尔滨医科大学附属第二医院老年病科，哈尔滨 150086 ） 【摘 要】FoxO转录因子是PKB/Akt 的下游靶点。Akt调节细胞生存和增殖。Akt磷酸化FoxO抑制FoxO 的转录功能，促 进细胞生存、生长和增殖。在癌症中FoxO在不同的细胞信号通路中发挥重要作用。FoxO通过两个途径抑制凋亡信号， 促进细胞生长，其包括线粒体靶点蛋白Bcl12家族的多种前凋亡成员的表达、死亡受体配体如Fas配体和肿瘤坏死因子 相关凋亡诱导配体（TRAIL ）的表达，或是增加各种细胞周期蛋白依赖性激酶抑制蛋白的水平。本文主要概括了Akt/FoxO 调节细胞生长和生存的机制，以期为抗癌治疗提供新的可能。 【关键词】FoxO ；Akt ；细胞凋亡 【中图分类号】 R329.25 【文献标识码】 A 【DOI 】 10.3724/SP.J.1264.2013.0024 1 Role of Akt/FoxO pathway in regulation of cell apoptosis * YAO Yue, MENG Jia, JIANG Li-Hong, ZHANG Yi-Na (Department of Geriatrics, the Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China) 【Abstract 】 The transcription factor FoxO is a downstream target of PKB/Akt that regulates cell survival and proliferation. Phosphorylation of FoxO by Akt inhibits its own transcriptional function and thus promotes cell survival, growth and proliferation. Substantial evidence showed that FoxO plays vital roles in diverse cellular signaling pathways that are implicated in cancer. There are two means by which FoxO inhibited cell apoptosis and promoted cell growth. One means is to regulate the expression of members of mitochondrial Bcl12 family, Fas ligands and tumor necrosis factor related apoptosis inducing ligand (TRAIL). The other is to enhance the level of cyclin-dependent kinase inhibitors . In this paper, we reviewed the underlying mechanisms of the involvement of Akt/FoxO in the regulation of cell survival and growth in order to provide new options for anti-tumor therapy. 【Key words 】 FoxO; Akt; apoptosis This work was supported by the Science and Technology Research Project of Educational Commission of Heilongjiang Province ( 1252Z019). Corresponding author: ZHANG Yi-N