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

Sarita Jena, Wai-Ping Lee, Declan Doherty, Paul D Thompson

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume132
Issue number1-2
DOIs
Publication statusPublished - Oct 2012

Bibliographical note

Copyright © 2012 Elsevier Ltd. All rights reserved.

Keywords

  • Cytochrome P-450 CYP3A/genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Protein Inhibitors of Activated STAT/metabolism
  • Receptors, Calcitriol/metabolism
  • Signal Transduction
  • Small Ubiquitin-Related Modifier Proteins/metabolism
  • Steroid Hydroxylases/genetics
  • Ubiquitin-Protein Ligases/metabolism
  • Vitamin D3 24-Hydroxylase

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