Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Cell Mol Life Sci. 2013 Jun;70(11):1897-913. doi: 10.1007/s00018-012-1144-9. Epub 2012 Sep 13.
The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.
EYA 蛋白最初在果蝇眼睛发育的背景下被描述，现在与器官发育、先天免疫、DNA 损伤修复、光周期、血管生成和癌症转移等截然不同的过程有关。这些功能与不寻常的生化活性组合有关：在不同的结构域中具有酪氨酸磷酸酶和苏氨酸磷酸酶活性，以及与 DNA 结合伴侣结合时的转录激活潜力。EYA 突变与多器官发育障碍以及从扩张型心肌病到迟发性感觉神经性听力损失的成年疾病有关。随着对 EYA 生化和细胞活性、生物学功能以及与疾病的关联的理解不断加深，EYA 蛋白有可能适合设计靶向治疗药物。结构信息的可用性、与疾病状态的直接联系、可用的动物模型，以及它们利用非传统的反应机制以实现特异性的事实表明，EYA 蛋白非常适合药物发现工作。本文综述了 EYA 的结构、活性和功能，以及它们与发育和疾病的关系，特别强调了最近的发现。
