SUMOylation Status and Effects of SUMylation on DAX-1

DAX-1 (Dosage Sensitive Sex Reversal Adrenal Hypoplasia Congenita on the X Chromosome gene 1) is a Nuclear Hormone Receptor, which acts as a transcriptional repressor in the nucleus. DAX-1 plays an important role in development and also appears to have some influence on the progression of cancer. In an effort to better understand DAX-1 function both in normal and disease states we are examining one type of posttranslational modification, SUMOylation. SUMOylation involves the addition of the small polypeptide conjugate SUMO (Small Ubiquitin-like Modifier) to proteins, this can have a variety of effects on protein activity. To study the effects of SUMOylation on DAX-1, the overall SUMOylation status of DAX-1 in mammalian cell lines was determined. It was found that DAX-1 is SUMOylated in several cell lines, both normal and carcinoma cells. Mutations were made in putative SUMOylation sites within the DAX-1 gene and assayed for changes in gene expression and activity.