PMID- 8721985
OWN - NLM
STAT- MEDLINE
DCOM- 19961008
LR  - 20220317
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 10
IP  - 4
DP  - 1996 Apr
TI  - Retinoid X receptor isotype identity directs human vitamin D receptor heterodimer 
      transactivation from the 24-hydroxylase vitamin D response elements in yeast.
PG  - 408-19
AB  - Unlike estrogen and progesterone receptors that operate as homodimers on response 
      elements, retinoid X receptors (RXRs) and vitamin D receptors (VDRs) can function 
      as heterodimers. Studies concerning the significance of heterodimeric 
      partnerships are usually performed utilizing mammalian or insect cells. These 
      cells express endogenous nuclear receptors, making it impossible to assign a role 
      for one receptor subtype over another while studying the function of transfected 
      receptor(s). Yeast lacks endogenous VDRs and RXRs and their ligands and provides 
      a unique cellular context to study nuclear receptor function. We examined the 
      interaction between human VDR and human RXR alpha, mouse RXR beta 2, and mouse 
      RXR gamma to identify physiologically important receptor interactions. DNA 
      binding studies on consensus, osteocalcin, or the rat 24-hydroxylase vitamin D 
      response elements (VDREs) indicated that although RXR complexes can form on the 
      consensus DNA elements, RXR:VDR heterodimers preferentially interact with the 
      natural VDREs. The interaction is RXR isotype-specific and affected by ligands. 
      Transactivation studies using the rat 24-hydroxylase VDREs indicated that VDR 
      preferentially associated with RXR alpha or RXR gamma to stimulate transcription, 
      and the activity was potentiated by ligand. Although RXR beta 2:VDR bound tightly 
      to DNA, the resulting heterodimer transactivated poorly. The regulation of the 
      24-hydroxylase promoter observed in yeast is similar with respect to 
      transactivation potential of specific VDRE and fold activation observed in 
      osteosarcoma cells. Ligand binding to both receptors in a RXR:VDR complex is 
      required for maximal transcriptional activity, indicating that the 
      isotype-specific RXR partner significantly contributes to the ability of RXR:VDR 
      heterodimers to transactivate from target response elements in yeast.
FAU - Kephart, D D
AU  - Kephart DD
AD  - Department of Molecular Virology, SmithKline Beecham Pharmaceuticals, King of 
      Prussia, Pennsylvania 19406-0939, USA.
FAU - Walfish, P G
AU  - Walfish PG
FAU - DeLuca, H
AU  - DeLuca H
FAU - Butt, T R
AU  - Butt TR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 104982-03-8 (Osteocalcin)
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)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cytochrome P-450 Enzyme System/*biosynthesis/genetics
MH  - DNA-Binding Proteins/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - Osteocalcin/biosynthesis/genetics
MH  - Rats
MH  - Receptors, Calcitriol/chemistry/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Recombinant Proteins/biosynthesis/metabolism
MH  - Retinoid X Receptors
MH  - Saccharomyces cerevisiae/*metabolism
MH  - Steroid Hydroxylases/*biosynthesis/genetics
MH  - TATA Box
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - *Transcriptional Activation
MH  - Transfection
MH  - Vitamin D3 24-Hydroxylase
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1210/mend.10.4.8721985 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1996 Apr;10(4):408-19. doi: 10.1210/mend.10.4.8721985.