MiT/TFE Family of Transcription Factors: An Evolutionary Perspective

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.

Automated summary

Response and adaptation to stress are crucial for survival, and regulation of the transcriptional machinery by the MiT/TFE family of transcription factors is an important aspect of this process. These proteins, conserved through evolution, play key roles in cellular functions in response to various stresses. Their tissue expression and activities are highly regulated by alternative splicing, promoter usage, and posttranslational modifications. The study of MiT/TFE proteins and their transcriptional regulatory mechanisms is important for potential therapeutic targets in human diseases like lysosomal storage disorders, neurodegeneration, and cancer.