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叉头框O(FOXO)转录因子在衰老和疾病中的作用。

Role of Forkhead Box O (FOXO) transcription factor in aging and diseases.

作者信息

Tia Neelam, Singh Alok Kumar, Pandey Poorti, Azad Chandra Shekhar, Chaudhary Pritee, Gambhir Indrajeet Singh

机构信息

Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.

Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.

出版信息

Gene. 2018 Mar 30;648:97-105. doi: 10.1016/j.gene.2018.01.051. Epub 2018 Feb 4.

Abstract

Fork head box O (FOXO) transcription factor is a key player in an evolutionarily conserved pathway. The mammalian FOXO family consists of FOXO1, 3, 4 and 6, are highly similar in their structure, function and regulation. To maintain optimum body function, the organisms have developed complex mechanisms for homeostasis. Importantly, it is well known that when these mechanisms dysregulate it results in the development of age-related disease. FOXO proteins are involved in a diverse cellular function and also have clinical significance including cell cycle arrest, cell differentiation, tumour suppression, DNA repair, longevity, diabetic complications, immunity, wound healing, regulation of metabolism and thus treatment of several types of diseases. By the combinations of post-translational modifications FOXO's serve as a 'molecular code' to sense external stimuli and recruit it as to specific regions of the genome and provide an integrated cellular response to changing physiological conditions. Akt/Protein kinase B a signaling pathway as a main regulator of FOXO to perform a diverse function in organisms. The present review summarizes the molecular and clinical aspects of FOXO transcription factor. And also elaborate the interaction of FOXO with the nucleosome remodelling complex to target genes, which is essential to cellular homeostasis.

摘要

叉头框O(FOXO)转录因子是进化保守通路中的关键因子。哺乳动物的FOXO家族由FOXO1、3、4和6组成,它们在结构、功能和调控方面高度相似。为维持最佳身体功能,生物体已发展出复杂的体内平衡机制。重要的是,众所周知,当这些机制失调时会导致与年龄相关疾病的发生。FOXO蛋白参与多种细胞功能,在临床上也具有重要意义,包括细胞周期停滞、细胞分化、肿瘤抑制、DNA修复、长寿、糖尿病并发症、免疫、伤口愈合、代谢调节,因而可用于多种疾病的治疗。通过翻译后修饰的组合,FOXO充当“分子密码”来感知外部刺激,并将其募集到基因组的特定区域,从而对不断变化的生理条件做出综合细胞反应。Akt/蛋白激酶B信号通路作为FOXO的主要调节因子,在生物体中发挥多种功能。本综述总结了FOXO转录因子的分子和临床方面。此外,还阐述了FOXO与核小体重塑复合物对靶基因的相互作用,这对细胞内稳态至关重要。

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