PMID- 10196214
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Vitamin D-dependent suppression of human atrial natriuretic peptide gene promoter 
      activity requires heterodimer assembly.
PG  - 11260-6
AB  - Crystallographic structures of the ligand-binding domains for the retinoid X 
      (RXR) and estrogen receptors have identified conserved surface residues that 
      participate in dimer formation. Homologous regions have been identified in the 
      human vitamin D receptor (hVDR). Mutating Lys-386 to Ala (K386A) in hVDR 
      significantly reduced binding to glutathione S-transferase-RXRalpha in solution, 
      whereas binding of an I384R/Q385R VDR mutant was almost undetectable. The K386A 
      mutant formed heterodimers with RXRalpha on DR-3 (a direct repeat of AGGTCA 
      spaced by three nucleotides), whereas the I384R/Q385R mutant completely 
      eliminated heterodimer formation. Wild type hVDR effected a 3-fold induction of 
      DR-3-dependent thymidine kinase-luciferase activity in cultured neonatal rat 
      atrial myocytes, an effect that was increased to 8-9-fold by cotransfected 
      hRXRalpha. Induction by K386A, in the presence or absence of RXRalpha, was only 
      slightly lower than that seen with wild type VDR. On the other hand, I384R/Q385R 
      alone displayed no stimulatory activity and less than 2-fold induction in the 
      presence of hRXRalpha. Qualitatively similar findings were observed with the 
      negative regulation of the human atrial natriuretic peptide gene promoter by 
      these mutants. Collectively, these studies identify specific amino acids in hVDR 
      that play a critical role in heterodimer formation and subsequent modulation of 
      gene transcription.
FAU - Chen, S
AU  - Chen S
AD  - Metabolic Research Unit and Department of Medicine, University of California, San 
      Francisco, California 94143-0540, USA.
FAU - Costa, C H
AU  - Costa CH
FAU - Nakamura, K
AU  - Nakamura K
FAU - Ribeiro, R C
AU  - Ribeiro RC
FAU - Gardner, D G
AU  - Gardner DG
LA  - eng
GR  - HL-35753/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 1406-16-2 (Vitamin D)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Atrial Natriuretic Factor/*genetics
MH  - Dimerization
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - *Promoter Regions, Genetic
MH  - Protein Conformation
MH  - Rats
MH  - Receptors, Calcitriol/chemistry/genetics
MH  - Receptors, Retinoic Acid/chemistry/genetics
MH  - Retinoid X Receptors
MH  - Sequence Homology, Amino Acid
MH  - Transcription Factors/chemistry/genetics
MH  - Transcription, Genetic
MH  - Vitamin D/*pharmacology
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - S0021-9258(19)73633-3 [pii]
AID - 10.1074/jbc.274.16.11260 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):11260-6. doi: 10.1074/jbc.274.16.11260.