转录调控因子Fox的功能及分子机制研究进展

Progress in functions and molecular mechanisms of the transcription factor Fox

Fox(Forkhead box)蛋白家族有19个亚族,它们通过结合DNA,激活或抑制目的基因的转录活性,同时还能参与细胞信号转导、细胞周期调控和新陈代谢的调节,在生物体发育及其成熟的组织器官中均能发挥重要作用,目前,有关Fox蛋白家族的功能及分子机制已逐步成为免疫学、遗传学、医学以及肿瘤学领域的研究热点。本文综述了Fox家族成员的命名及分类、蛋白结构及其DNA识别机制以及该家族成员如何参与Hh,TGF-β/SMAD,MAPK,Wnt/β-catenin和IGF信号通路的调控。Fox家族可调控线虫的咽、果蝇的唾液腺以及哺乳动物的肝脏和眼睛等器官的发育,能够影响细胞周期,其家族成员FoxA可以和CREB、GR结合调控新陈代谢。不同物种的Fox家族成员个数存在差异,并且受到严格的进化选择。对其功能和分子进化机制进一步研究可为阐明生物的发育机理和人类疾病的防治提供新的思路。

Fox （Forkhead box） protein family has 19 subfamilies. The members of these subfamilies are able to bind DNA, activate or inhibit the transcriptional activity of target gene, and can participate in cellular signal transduction, cell cycle role in the development of organisms regulation and metabolism regulation. Meanwhile, they play a key and their mature tissues and organs. Nowadays, the study of the function and molecular mechanism of Fox is gradually becoming a research hotspot in the fields of immunology, genetics, medicine and ontology. In this review, we summarized the nomenclature, the classification and the protein structure of the Fox and its functions on signal transduction pathways including the Hh, TGF-β/SMAD, MAPK, Wnt/β-catenin and IGF. The Fox family can regulate the development of many organs, such as the pharynx of Caenorhabditis elegans, the salivary gland of Drosophila melanogaster and the liver and eye of mammals. Fox is able to affect the cell cycle, and FoxA can regulate the metabolism by binding with CREB and GR. The copy number of Fox varies in different species and is subjected to strict evolutionary selection. The further research on the functions and molecular evolutionary mechanisms of the Fox genes will shed new insights into understanding the developmental mechanisms of organisms and the prevention and treatment of human diseases.