2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 49(2015) N 1 p. 65-76; DOI 10.1134/S0026893315010124 Full Text

A.S. Orekhova1, P.M. Rubtsov1,2*

DAX1, an unusual member of the nuclear receptor superfamily with diverse functions

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow region, 141700 Russia

Received - 2014-09-01; Accepted - 2014-09-03

Nuclear receptors (NRs) act as ligand-activated transcription factors and play an important role in regulating metabolism, homeostasis, differentiation, development, and pathogenesis of various diseases. Once activated by a ligand, a NR binds to a specific nucleotide sequence in a target gene to activate its expression. Natural ligands are known for the majority of NRs. DAX1 is an unusual member of the NR superfamily, lacking a ligand and a typical DNA-binding domain. DAX1 was found to play an important role in regulating the development of the adrenals and gonads as early as 20 years ago, but the molecular mechanisms of its effect were unclear. DAX1 is capable of interacting with many members of the NR superfamily and with various transcriptional corepressors and coactivators, and its functions are not restricted to regulating the adrenal and gonadal development and contributing to steroidogenesis. Recent studies elucidated the role DAX1 plays in the pathogenesis of X-linked adrenal hypoplasia and dosage-sensitive sex reversal. DAX1 is an important component of the transcription factor network that maintains the pluripotent state of mouse embryonic stem cells. Modern data on the properties, functions, and mechanisms of action of DAX1 are considered in the review. Specifics of the DAX1 interactions with various protein partners are characterized. Examples are provided to illustrate the corepressor and coactivator effects of DAX1 on target gene transcription. In addition, the review discusses the role DAX1 plays in the pathogenesis of hereditary disorders, a possible association of DAX1 with endocrine oncology diseases, and the contribution of DAX1 to self-renewal of mouse embryonic stem cells.

nuclear receptors, DAX1 (NR0B1), transcription factors, transcriptional repressors, protein-protein interactions, gene expression, steroidogenesis, cell differentiation, X-linked congenital adrenal hypoplasia, dosage-sensitive sex reversal, embryonic stem cells, pluripotency