PMID- 8579895
OWN - NLM
STAT- MEDLINE
DCOM- 19960320
LR  - 20220408
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 17
IP  - 2 Suppl
DP  - 1995 Aug
TI  - New understanding of the molecular mechanism of receptor-mediated genomic actions 
      of the vitamin D hormone.
PG  - 33S-38S
AB  - The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3 
      [1,25(OH)2D3]hormone with high affinity and elicits its actions to regulate gene 
      expression in target cells by binding to vitamin D-responsive elements (VDREs). 
      VDREs in positively controlled genes such as osteocalcin, osteopontin, beta 
      3-integrin, and vitamin D-24-OHase are direct hexanucleotide repeats with a 
      spacer of three nucleotides. The VDR associates with these VDREs with the 
      greatest affinity as a heterodimer with one of the family of retinoid X receptors 
      (RXRs). VDR consists of an N-terminal zinc finger domain that determines DNA 
      binding, a "hinge" segment and a C-terminal hormone binding domain which also 
      contains two conserved regions that engage in heterodimerization with an RXR on 
      the VDRE. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the 
      VDR-RXR heterodimer is to alter the conformation of the hormone-binding domain of 
      VDR to facilitate strong dimerization with RXR, which results in ligand-enhanced 
      association with the VDRE. Thus RXR is recruited into a heterocomplex by liganded 
      VDR. The natural ligand for the RXR coreceptor, 9-cis retinoic acid, suppresses 
      both VDR-RXR binding to the VDRE and 1,25(OH)2D3-stimulated transcription, 
      indicating that 9-cis retinoic acid diverts RXR away from being the silent 
      partner of VDR to instead form RXR homodimers. Recent data reveal that after 
      binding RXR, a subsequent target for VDR in the vitamin D signal transduction 
      cascade is basal transcription factor IIB (TFIIB).(ABSTRACT TRUNCATED AT 250 
      WORDS)
FAU - Haussler, M R
AU  - Haussler MR
AD  - Department of Biochemistry, College of Medicine, University of Arizona, Tucson 
      85724, USA.
FAU - Jurutka, P W
AU  - Jurutka PW
FAU - Hsieh, J C
AU  - Hsieh JC
FAU - Thompson, P D
AU  - Thompson PD
FAU - Selznick, S H
AU  - Selznick SH
FAU - Haussler, C A
AU  - Haussler CA
FAU - Whitfield, G K
AU  - Whitfield GK
LA  - eng
GR  - AR15781/AR/NIAMS NIH HHS/United States
GR  - DK33351/DK/NIDDK NIH HHS/United States
GR  - DK40372/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Integrins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (SPP1 protein, human)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, rat)
RN  - 0 (Transcription Factors)
RN  - 104982-03-8 (Osteocalcin)
RN  - 106441-73-0 (Osteopontin)
RN  - 1406-16-2 (Vitamin D)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Calcitriol/chemistry/metabolism/*pharmacology
MH  - Chickens
MH  - *Cytochrome P-450 Enzyme System
MH  - DNA/metabolism
MH  - Gene Expression Regulation/drug effects/*genetics
MH  - Humans
MH  - Integrins/genetics
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Osteocalcin/genetics
MH  - Osteopontin
MH  - Rats
MH  - Receptors, Calcitriol/chemistry/drug effects/*metabolism/physiology
MH  - Receptors, Retinoic Acid/genetics/metabolism
MH  - Retinoid X Receptors
MH  - Sialoglycoproteins/genetics
MH  - Steroid Hydroxylases/genetics
MH  - Structure-Activity Relationship
MH  - Transcription Factors/genetics/metabolism
MH  - Transcriptional Activation/*genetics
MH  - Tretinoin/metabolism
MH  - Vitamin D/chemistry/metabolism/*physiology
MH  - Vitamin D3 24-Hydroxylase
RF  - 30
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - 8756-3282(95)00205-R [pii]
AID - 10.1016/8756-3282(95)00205-r [doi]
PST - ppublish
SO  - Bone. 1995 Aug;17(2 Suppl):33S-38S. doi: 10.1016/8756-3282(95)00205-r.