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    J Steroid Biochem Mol Biol. 2012 Oct;132(1-2):24-31. Epub 2012 Apr 27.

    PIAS4 represses vitamin D receptor-mediated signaling and acts as an E3-SUMO ligase towards vitamin D receptor.

    Source

    School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.

    Abstract

    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.

    Copyright © 2012 Elsevier Ltd. All rights reserved.

    PMID:
    22564762
    [PubMed - in process]

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