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Submitted on May 13, 2003
Accepted on March 16, 2004
Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
* To whom correspondence should be addressed. E-mail: gsaunders{at}mdanderson.org.
DAX-1 (dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1; NR0B1) is an orphan nuclear receptor that plays an important role in the development and functioning of the adrenal gland and hypothalamic-pituitary gonadal axis. The DAX-1 protein acts as a transcriptional repressor of genes involved in the steroidogenic pathway. We have identified a novel isoform encoded by the known exon 1 of DAX-1 and a previously unrecognized exon (exon 2
) that lies within intron 1 of DAX-1. This novel transcript, which we designated DAX-1, is terminates at exon 2; the last 70 amino acids of the C-terminal repressor domain encoded by exon 2 are absent. DAX-1 encodes a protein of 401 amino acids; the first 389 amino acids are encoded by exon 1 and the last 12 by exon 2. Using conventional RT-PCR and real-time RT-PCR analyses, we found that DAX-1 is abundantly expressed in the adrenal gland, brain, kidney, ovary, and testis. We also found that DAX-1 can bind to steroidogenic factor 1 (SF-1) and to DNA but is unable to repress SF-1-mediated transcriptional activation of the reporter gene and acts as an antagonist of DAX-1 under certain conditions.
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