Functional characterization of a novel type of 1 alpha,25-dihydroxyvitamin D-3 response element identified in the mouse c-fos promoter

被引:33
作者
Schrader, M [1 ]
Kahlen, JP [1 ]
Carlberg, C [1 ]
机构
[1] UNIV GENEVA,HOP CANTONAL,DERMATOL CLIN,CH-1211 GENEVA 14,SWITZERLAND
关键词
D O I
10.1006/bbrc.1996.6025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The seco-steroid 1 alpha,25-dihydroxyvitamin D-3 (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. (C) 1997 Academic Press
引用
收藏
页码:646 / 651
页数:6
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