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Nuclear receptors (NRs) are ligand-activated transcription factors that play an important role in metabolism, homeostasis, differentiation and development regulation. NRs are also involved in pathogenesis of various diseases. For most of NRs natural ligands are known. Ligand-activated NRs bind specific nucleotide sequences in target genes and induce their expression. DAX1 protein is an unusual member of NR superfamily that does not have ligand and lacks typical DNA-binding domain. It was established 20 years ago that DAX1 plays a critical role in regulation of adrenal and gonadal development and in biosynthesis of steroid hormones, however the molecular mechanisms of its action remained not fully understood. Further studies have shown that this piotein can interact with many members of NR superfamily and with different co-repressors and co-activators of transcription. Its functions are not restricted to regulation of adrenal and gonadal development and steroidogenesis. Recent studies have elucidated the role of DAX1 in pathogenesis of X-linked adrenal congenital hypoplasia and dose-sensitive sex reversal. It was found also that DAX1 is an important component of transcription factors network that maintains the pluripotency of mouse embryonic stem Cells. Here we review the current knowledge on properties, functions and mechanisms of DAX1 action. The role of DAX1 in pathogenesis of inherited diseases is discussed. The specificity of DAX1 interaction with various protein.partners is characterized. The examples of co-repressor and coactivator action of DAX1 on transcription are presented. The potential association of DAX1 with oncoendocrine pathologies and its role in self-renewal of mouse embryonic stem cells are described.

Citation

A S Orekhova, P M Rubtsov. DAX1-unusual member of nuclear receptors superfamily with diverse functions]. Molekuliarnaia biologiia. 2015 Jan-Feb;49(1):75-88

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PMID: 25916112

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