Atoh8 in Development and Disease

SIMPLE SUMMARY: bHLH transcription factors control a variety of functions during development and disease. Atoh8 is one such bHLH factor with unique characteristics in the ‘atonal’ family. Consistent with the other homologs of its family, Atoh8 was identified to regulate cell fate and differentiation during development. Furthermore, it was also found to regulate other mechanisms in adult and mature organisms such as cancer, iron homeostasis and stress response. This review systematically outlines the role of Atoh8 in development and pathologies. At the same time, this review also anticipates its potential involvement in basic cellular mechanisms such as proliferation, metabolism, apoptosis and autophagy. ABSTRACT: Atoh8 belongs to a large superfamily of transcriptional regulators called basic helix-loop-helix (bHLH) proteins. bHLH proteins have been identified in a wide range of organisms from yeast to humans. The members of this special group of transcription factors were found to be involved not only in embryonic development but also in disease initiation and its progression. Given their importance in several fundamental processes, the translation, subcellular location and turnover of bHLH proteins is tightly regulated. Alterations in the expression of bHLH proteins have been associated with multiple diseases also in context with Atoh8 which seems to unfold its functions as both transcriptional activator and repressor. Like many other bHLH transcription factors, so far, Atoh8 has also been observed to be involved in both embryonic development and carcinogenesis where it mainly acts as tumor suppressor. This review summarizes our current understanding of Atoh8 structure, function and regulation and its complex and partially controversial involvement in development and disease.