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
相关论文
共 39 条
  • [1] THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION
    ANGEL, P
    KARIN, M
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) : 129 - 157
  • [2] CLONING AND EXPRESSION OF FULL-LENGTH CDNA-ENCODING HUMAN VITAMIN-D RECEPTOR
    BAKER, AR
    MCDONNELL, DP
    HUGHES, M
    CRISP, TM
    MANGELSDORF, DJ
    HAUSSLER, MR
    PIKE, JW
    SHINE, J
    OMALLEY, BW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (10) : 3294 - 3298
  • [3] STRUCTURE-FUNCTION-RELATIONSHIPS IN THE VITAMIN-D ENDOCRINE SYSTEM
    BOUILLON, R
    OKAMURA, WH
    NORMAN, AW
    [J]. ENDOCRINE REVIEWS, 1995, 16 (02) : 200 - 257
  • [4] DIFFERENTIAL STIMULATION OF FOS AND JUN FAMILY MEMBERS BY CALCITRIOL IN OSTEOBLASTIC CELLS
    CANDELIERE, GA
    PRUDHOMME, J
    STARNAUD, R
    [J]. MOLECULAR ENDOCRINOLOGY, 1991, 5 (12) : 1780 - 1788
  • [5] Candeliere GA, 1996, MOL CELL BIOL, V16, P584
  • [6] THE 1,25-DIHYDROXYVITAMIN D-3 (VD) ANALOGS MC903, EB1089 AND KH1060 ACTIVATE THE VD RECEPTOR - HOMODIMERS SHOW HIGHER LIGAND SENSITIVITY THAN HETERODIMERS WITH RETINOID X RECEPTORS
    CARLBERG, C
    MATHIASEN, IS
    SAURAT, JH
    BINDERUP, L
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1994, 51 (3-4) : 137 - 142
  • [7] The antiproliferative effect of vitamin D-3 analogues
    Carlberg, C
    [J]. DERMATOLOGY, 1996, 192 (03) : 195 - 197
  • [8] 2 NUCLEAR SIGNALING PATHWAYS FOR VITAMIN-D
    CARLBERG, C
    BENDIK, I
    WYSS, A
    MEIER, E
    STURZENBECKER, LJ
    GRIPPO, JF
    HUNZIKER, W
    [J]. NATURE, 1993, 361 (6413) : 657 - 660
  • [9] MECHANISMS OF NUCLEAR SIGNALING BY VITAMIN-D-3 - INTERPLAY WITH RETINOID AND THYROID-HORMONE SIGNALING
    CARLBERG, C
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 231 (03): : 517 - 527
  • [10] CARLBERG C, 1996, ENDOCRINE, V4, P912