Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1991577 | The Journal of Steroid Biochemistry and Molecular Biology | 2012 | 8 Pages |
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.
► PIAS4 represses VDR transcriptional activity. ► PIAS4 interacts with unliganded VDR. ► PIAS4 facilitates modification of VDR with SUMO2. ► PIAS4 enhances VDR protein stability.