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Convergence of vitamin D and retinoic acid signalling at a common hormone response element
Author(s) -
TaveraMendoza Luz,
Wang TianTian,
Lallemant Benjamin,
Zhang Rui,
Nagai Yoshihiko,
Bourdeau Véronique,
RamirezCalderon Mario,
Desbarats Julie,
Mader Sylvie,
White John H
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400594
Subject(s) - retinoic acid , biology , microbiology and biotechnology , calcitriol receptor , crosstalk , transcription factor , retinoic acid receptor , nuclear receptor , receptor , cancer research , gene , biochemistry , physics , optics
Although 1,25‐dihydroxyvitamin D 3 (1,25D 3 ) 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 1,25D 3 and/or RA. Notably, an element was characterized in the cyclin‐dependent kinase (CDK) inhibitor p19 ink4d gene, and 1,25D 3 ‐ or RA‐induced p19 INK4D expression. P19 ink4d knockdown together with depletion of p27 kip1 , another CDK inhibitor regulated by 1,25D 3 and RA, rendered cells resistant to ligand‐induced growth arrest. Remarkably, p19 INK4D ‐deficient cells showed increased autophagic cell death, which was markedly enhanced by 1,25D 3 , but not RA, and attenuated by loss of p27 KIP1 . These results show a limited crosstalk between 1,25D 3 and RA signalling by means of overlapping nuclear receptor DNA binding specificities, and uncover a role for p19 INK4D in control of cell survival.