Martelli Alberto M, Tabellini Giovanna, Bressanin Daniela, Ognibene Andrea, Goto Kaoru, Cocco Lucio, Evangelisti Camilla
Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
Biochim Biophys Acta. 2012 Dec;1823(12):2168-78. doi: 10.1016/j.bbamcr.2012.08.017. Epub 2012 Aug 31.
Akt is a central player in the signal transduction pathways activated in response to many growth factors, hormones, cytokines, and nutrients and is thought to control a myriad of cellular functions including proliferation and survival, autophagy, metabolism, angiogenesis, motility, and exocytosis. Moreover, dysregulated Akt activity is being implicated in the pathogenesis of a growing number of disorders, including cancer. Evidence accumulated over the past 15 years has highlighted the presence of active Akt in the nucleus, where it acts as a fundamental component of key signaling pathways. For example, nuclear Akt counteracts apoptosis through a block of caspase-activated DNase: deoxyribonuclease and inhibition of chromatin condensation, and is also involved in cell cycle progression control, cell differentiation, mRNA: messenger RNA export, DNA repair, and tumorigenesis. In this review, we shall summarize the most relevant findings about nuclear Akt and its functions.
Akt是响应多种生长因子、激素、细胞因子和营养物质而激活的信号转导通路中的核心参与者,被认为可控制众多细胞功能,包括增殖与存活、自噬、代谢、血管生成、迁移和胞吐作用。此外,Akt活性失调与越来越多的疾病(包括癌症)的发病机制有关。过去15年积累的证据突出表明细胞核中存在活性Akt,它在其中作为关键信号通路的基本组成部分发挥作用。例如,核Akt通过阻断半胱天冬酶激活的脱氧核糖核酸酶(DNase)和抑制染色质凝聚来对抗细胞凋亡,还参与细胞周期进程控制、细胞分化、信使核糖核酸(mRNA)输出、DNA修复和肿瘤发生。在本综述中,我们将总结有关核Akt及其功能的最相关研究发现。