文章：

叉头盒蛋白：转录和谐的音叉

Forkhead box proteins: tuning forks for transcriptional harmony

原文发布日期：2013-06-24

DOI: 10.1038/nrc3539

类型: Review Article

开放获取: 否

要点：

1. Forkhead box (FOX) proteins are a superfamily of transcriptional regulators that have a key role both during development and in adult tissue homeostasis. Fifty human FOX proteins related through their 'forkhead' or 'winged-helix' DNA-binding domain (DBD) have been discovered, and they are further divided into 19 subfamilies (FOXA to FOXS) on the basis of sequence homology within and outside their forkhead domain.
2. Forkhead transcription factors, in particular FOXA, FOXC, FOXM, FOXO and FOXP proteins, are essential components of oncogenic and tumour suppressive pathways.
3. Deregulation of FOX proteins has a direct role in cancer initiation, maintenance, progression and drug resistance.
4. Control of various FOX family members is not only achieved through cell-specific expression, but is also fine-tuned by a myriad of post-translational modifications and through interactions with specific cofactors.
5. Besides being conventional transcriptional activators, FOX proteins also function as transcriptional repressors, pioneer factors, and they modulate and cooperate with other transcription factors and epigenetic effectors.
6. A better understanding of the mechanistic complexities that govern the regulation and functions of these FOX transcription factors should help us to realize their potential as therapeutic targets, as well as reliable predictive markers for cancer.

要点翻译：

1. 叉头框（FOX）蛋白是一个转录调节因子超家族，在发育过程和成年组织稳态维持中均发挥关键作用。目前已发现50种人类FOX蛋白，它们均通过其“叉头”或“翼状螺旋”DNA结合结构域（DBD）相关联，并根据叉头结构域内外的序列同源性进一步划分为19个亚家族（FOXA至FOXS）。
2. 叉头转录因子，特别是FOXA、FOXC、FOXM、FOXO和FOXP蛋白，是致癌和肿瘤抑制通路的重要组成部分。
3. FOX蛋白的失调在癌症发生、维持、进展及耐药性中具有直接作用。
4. 对各类FOX家族成员的调控不仅通过细胞特异性表达实现，还通过大量翻译后修饰以及与特定辅因子的相互作用进行微调。
5. 除作为常规转录激活因子外，FOX蛋白还兼具转录抑制因子、先驱因子等功能，并能调节其他转录因子和表观遗传效应物并与之协同作用。
6. 更深入地理解这些FOX转录因子调控与功能的复杂机制，将有助于我们挖掘其作为癌症治疗靶点及可靠预测标志物的潜力。

英文摘要：

Forkhead box (FOX) proteins are multifaceted transcription factors that are responsible for fine-tuning the spatial and temporal expression of a broad range of genes both during development and in adult tissues. This function is engrained in their ability to integrate a multitude of cellular and environmental signals and to act with remarkable fidelity. Several key members of the FOXA, FOXC, FOXM, FOXO and FOXP subfamilies are strongly implicated in cancer, driving initiation, maintenance, progression and drug resistance. The functional complexities of FOX proteins are coming to light and have established these transcription factors as possible therapeutic targets and putative biomarkers for specific cancers.

摘要翻译： 

叉头框（FOX）蛋白是多面性的转录因子，负责在发育过程中及成年组织中对大量基因的空间和时间表达进行精细调控。这一功能根植于其整合多种细胞和环境信号并以极高保真度行事的能力。FOXA、FOXC、FOXM、FOXO 和 FOXP 亚家族中的若干关键成员与癌症密切相关，驱动肿瘤的起始、维持、进展及耐药。FOX 蛋白的功能复杂性正逐渐显现，使这些转录因子成为特定癌症潜在的治疗靶点和候选生物标志物。

原文链接：

Forkhead box proteins: tuning forks for transcriptional harmony