La Spina Martina, Contreras Pablo S, Rissone Alberto, Meena Naresh K, Jeong Eutteum, Martina José A
Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Front Cell Dev Biol. 2021 Jan 6;8:609683. doi: 10.3389/fcell.2020.609683. eCollection 2020.
Response and adaptation to stress are critical for the survival of all living organisms. The regulation of the transcriptional machinery is an important aspect of these complex processes. The members of the microphthalmia (MiT/TFE) family of transcription factors, apart from their involvement in melanocyte biology, are emerging as key players in a wide range of cellular functions in response to a plethora of internal and external stresses. The MiT/TFE proteins are structurally related and conserved through evolution. Their tissue expression and activities are highly regulated by alternative splicing, promoter usage, and posttranslational modifications. Here, we summarize the functions of MiT/TFE proteins as master transcriptional regulators across evolution and discuss the contribution of animal models to our understanding of the various roles of these transcription factors. We also highlight the importance of deciphering transcriptional regulatory mechanisms in the quest for potential therapeutic targets for human diseases, such as lysosomal storage disorders, neurodegeneration, and cancer.
对压力的反应和适应对所有生物的生存至关重要。转录机制的调控是这些复杂过程的一个重要方面。小眼症（MiT/TFE）转录因子家族成员，除了参与黑素细胞生物学外，正逐渐成为应对大量内部和外部压力时广泛细胞功能的关键参与者。MiT/TFE蛋白在结构上相关且在进化过程中保守。它们的组织表达和活性受到可变剪接、启动子使用和翻译后修饰的高度调控。在这里，我们总结了MiT/TFE蛋白作为跨进化的主要转录调节因子的功能，并讨论了动物模型对我们理解这些转录因子各种作用的贡献。我们还强调了在寻找人类疾病（如溶酶体贮积症、神经退行性变和癌症）潜在治疗靶点的过程中，破译转录调控机制的重要性。
