The present study investigated the potential for members of the protein inhibitors of activated STAT (PIAS) family to function as co-regulators of the vitamin D signal pathway. Among the PIAS proteins evaluated, we establish PIAS4 as a potent inhibitor of the transcriptional responses of the CYP3A4 and CYP24A1 target genes to the active hormonal form of vitamin D, a repression that was observed to be dependent upon an intact SUMO-ligase function of PIAS4. We report that PIAS4 represents a direct binding partner for vitamin D receptor (VDR) and also facilitates its modification with SUMO2, a process that preferentially occurs on the apo-form of VDR and which is reversed upon binding of ligand. Our results implicate PIAS4 and the process of SUMOylation as important modulators of VDR-mediated signaling which may both represent flexible mechanistic components as to how vitamin D achieves its pleiotropic effects.
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|Publication status||Published - Oct 2012|
Jena, S., Lee, W-P., Doherty, D., & Thompson, P. (2012). PIAS4 represses vitamin D receptor-mediated signaling and acts as an E3-SUMO ligase towards vitamin D receptor. Journal of Steroid Biochemistry and Molecular Biology, 132(1-2), 24-31. http://www.sciencedirect.com/science/article/pii/S096007601200091X