Schräder M, Kahlen J P, Carlberg C
Clinique de Dermatologie, Hôpital Cantonal Universitaire, Genève, Switzerland.
Biochem Biophys Res Commun. 1997 Jan 23;230(3):646-51. doi: 10.1006/bbrc.1996.6025.
The seco-steroid 1 alpha,25-dihydroxyvitamin D3 (VD) is known to inhibit cellular proliferation and to induce differentiation as well as programmed cell death (apoptosis). VD is the ligand of the transcription factor VDR, which is a member of the nuclear receptor superfamily. Primary VD responding genes contain a VD response element (VDRE), on which VDR binds as a dimeric complex. The main heterodimeric partner of VDR is the retinoid X receptor (RXR) and the majority of the known natural VDREs are formed by a direct repeat of hexameric core binding motifs spaced by 3 nucleotides. Most of the genes carrying DR3-type VDREs are associated with the hormone's classical function, which is the regulation of calcium homeostasis. Recently, it has been found that inverted palindromic arrangements spaced by 9 nucleotides also form functional VDREs. This paper reports the identification of a novel IP9-type VDRE in the mouse c-fos promoter. This elements is bound with high affinity by VDR-RXR heterodimers and responds at 10-fold lower concentrations to the potent anti-proliferative VD analogue EB1089 than to VD. This suggests that VD may be directly involved in the transcriptional regulation of the cell cycle via the activation of the c-fos gene.
已知甾体类化合物1α,25 - 二羟基维生素D3（VD）可抑制细胞增殖、诱导分化以及程序性细胞死亡（凋亡）。VD是转录因子VDR的配体，VDR属于核受体超家族成员。主要的VD应答基因含有一个VD应答元件（VDRE），VDR作为二聚体复合物与之结合。VDR的主要异源二聚体伴侣是视黄酸X受体（RXR），大多数已知的天然VDRE由间隔3个核苷酸的六聚体核心结合基序直接重复形成。大多数携带DR3型VDRE的基因与该激素的经典功能相关，即调节钙稳态。最近发现，间隔9个核苷酸的反向回文排列也能形成功能性VDRE。本文报道了在小鼠c - fos启动子中鉴定出一种新型的IP9型VDRE。该元件与VDR - RXR异源二聚体具有高亲和力结合，并且对强效抗增殖VD类似物EB1089的反应浓度比对VD的反应浓度低10倍。这表明VD可能通过激活c - fos基因直接参与细胞周期的转录调控。
