کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1991577 | 1541019 | 2012 | 8 صفحه PDF | دانلود رایگان |
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.
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 132, Issues 1–2, October 2012, Pages 24–31