Convergence of vitamin D and retinoic acid signalling at a common hormone response element

Department of Medicine, McGill University, 3655 Drummond St, Montreal, Quebec, Canada H3G 1Y6.
EMBO Reports (Impact Factor: 7.86). 03/2006; 7(2):180-5. DOI: 10.1038/sj.embor.7400594
Source: PubMed

ABSTRACT Although 1,25-dihydroxyvitamin D3 (1,25D3) and retinoic acid (RA) have distinct developmental and physiological roles, both regulate the cell cycle. We provide molecular and genomic evidence that their cognate nuclear receptors regulate common genes through everted repeat TGA(C/T)TPyN8PuG(G/T)TCA (ER8) response elements. ER8 motifs were found in the promoters of several target genes of 1,25D3 and/or RA. Notably, an element was characterized in the cyclin-dependent kinase (CDK) inhibitor p19ink4d gene, and 1,25D3- or RA-induced p19INK4D) expression. P19ink4d knockdown together with depletion of p27kip1, another CDK inhibitor regulated by 1,25D3 and RA, rendered cells resistant to ligand-induced growth arrest. Remarkably, p19INK4D-deficient cells showed increased autophagic cell death, which was markedly enhanced by 1,25D3, but not RA, and attenuated by loss of p27KIP1. These results show a limited crosstalk between 1,25D3 and RA signalling by means of overlapping nuclear receptor DNA binding specificities, and uncover a role for p19INK4D in control of cell survival.

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Available from: Benjamin Lallemant, Aug 12, 2015
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    • "VDRE elements are composed of tandem motifs having the consensus PuG(G/T)TCA, which are often arranged as direct repeats separated by 3 nucleotides (DR3-Type) [1] [3]. However, other types of VDREs, such as direct repeats with 4 spacing nucleotides (DR4-Type) or everted repeats with a spacer of 6–9 nucleotides (ER6-9) have been described [3] [6] [7]. This process is normally indicated as the " VDR genomic pathway " , in order to discern it from the " non genomic pathway " that is based on a putative 1,25(OH)2D3 surface receptor, followed by the activation of several intracellular transduction signaling cascades [3,8–10]. "
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