Forkhead box (FOX) proteins are an evolutionarily conserved family of transcription factors that play numerous regulatory roles in eukaryotes during developmental and adult life. Dysfunction of FOX proteins has been implicated in a variety of human diseases, including cancer, neurodevelopment disorders and genetic diseases. The FOX family members share a highly conserved DNA-binding domain (DBD), which is essential for DNA recognition, binding and function. Since the first FOX structure was resolved in 1993, >30 FOX structures have been reported to date. It is clear now that the structure and DNA recognition mechanisms vary among FOX members; however, a systematic review on this aspect is lacking. In this manuscript, we present an overview of the mechanisms by which FOX transcription factors bind DNA, including protein structures, DNA binding properties and disease-causing mutations. This review should enable a better understanding of FOX family transcription factors for basic researchers and clinicians.

中文翻译：

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对叉头转录因子对 DNA 结合的机械理解及其对致病突变的干扰

叉头盒 (FOX) 蛋白是一个进化上保守的转录因子家族，在真核生物的发育和成年生活中发挥着许多调节作用。FOX 蛋白的功能障碍与多种人类疾病有关，包括癌症、神经发育障碍和遗传疾病。FOX 家族成员共享一个高度保守的 DNA 结合域 (DBD)，这对于 DNA 识别、结合和功能至关重要。自从第一个 FOX 结构在 1993 年被解析以来，迄今为止已经报道了＞30 个 FOX 结构。现在很清楚，FOX 成员的结构和 DNA 识别机制各不相同。然而，缺乏对这方面的系统评价。在这份手稿中，我们概述了 FOX 转录因子结合 DNA 的机制，包括蛋白质结构，DNA结合特性和致病突变。这篇综述应该能让基础研究人员和临床医生更好地了解 FOX 家族转录因子。