Convergence of vitamin D and retinoic acid signalling at a common hormone response element
Convergence of vitamin D and retinoic acid signalling at a common hormone response element
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DOI：
10.1038/sj.embor.7400594
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发表时间：
2006-02-01
期刊：
影响因子：
7.7
通讯作者：
White, JH
中科院分区：
文献类型：
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作者：
Tavera-Mendoza, L;Wang, TT;White, JH
虽然1，25-二羟维生素D-3（1，25 D（3））和视黄酸（RA）具有不同的发育和生理作用，但两者都调节细胞周期。我们提供的分子和基因组证据表明，它们的同源核受体通过翻转重复TGA（C/T）TPyN 8 PuG（G/T）TCA（ER 8）反应元件调节共同的基因。在1，25 D3和/或RA的多个靶基因的启动子中发现了ER 8基序。值得注意的是，在细胞周期蛋白依赖性激酶（CDK）抑制剂p19（ink 4d）基因和1，25 D（3）或RA诱导的p19（INK 4D）表达中表征了一个元件。P19（ink 4d）的敲除与p27（kip 1）的耗尽一起，另一个由1，25 D3和RA调节的CDK抑制剂，使细胞抵抗配体诱导的生长停滞。值得注意的是，p19（INK 4D）缺陷的细胞表现出增加的自噬性细胞死亡，这是显着增强1，25 D3，但不是RA，并减弱损失的p27（KIP 1）。这些结果表明，通过重叠的核受体DNA结合特异性，1，25 D3和RA信号之间的有限串扰，并揭示了p19（INK 4D）在控制细胞存活中的作用。
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 1,25D3 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 1,25D3 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 1,25D3, but not RA, and attenuated by loss of p27(KIP1). 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 p19(INK4D) in control of cell survival.