PMID- 8908199
OWN - NLM
STAT- MEDLINE
DCOM- 19961210
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 169
IP  - 2
DP  - 1996 Nov
TI  - Inhibition of rabbit collagenase (matrix metalloproteinase-1; MMP-1) 
      transcription by retinoid receptors: evidence for binding of RARs/RXRs to the -77 
      AP-1 site through interactions with c-Jun.
PG  - 320-32
AB  - Treatment of synovial fibroblasts with retinoic acid (RA) decreases their 
      expression of collagenase (matrix metalloproteinase-1 or MMP-1), an enzyme that 
      degrades interstitial collagens and contributes to the pathology of rheumatoid 
      arthritis. This inhibition results, at least in part, from RA-induced decreases 
      in the mRNA for the transactivators Fos and Jun (with concominant increases in 
      RAR mRNA) and by sequestration of Fos/Jun by RARs/RXRs. Previously, we provided 
      evidence that retinoid receptors are also present in complexes that bind to 
      fragments of rabbit MMP-1 promoter DNA containing an AP-1 site at -77 (Pan et 
      al., 1995, J. Cell. Biochem., 57:575-589). However, it was unclear whether RARs 
      and retinoid X receptors (RXRs) were binding directly to the DNA or indirectly 
      through another protein. We now use a sensitive MMP-1 promoter/luciferase 
      reporter construct to confirm the transcriptional role of the AP-1 site at -77. 
      In addition, with electrophoretic mobility shift analyses (EMSAs), antibody 
      "supershifts" and DNAase 1 footprinting, we examine the interaction of retinoid 
      receptors and AP-1 protein on the MMP-1 promoter. We demonstrate that RARs, RXRs, 
      and c-Jun form a complex at the AP-1 site in which c-Jun binds directly to the 
      DNA and apparently tethers the retinoid receptors to the complex. We conclude 
      that retinoid receptors/AP-1 protein interactions at the DNA may provide an 
      additional means of controlling collagenase gene transcription by retinoids.
FAU - Schroen, D J
AU  - Schroen DJ
AD  - Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, 
      USA.
FAU - Brinckerhoff, C E
AU  - Brinckerhoff CE
LA  - eng
GR  - AR-26599/AR/NIAMS 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 Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (DNA Probes)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Collagenases/genetics/*metabolism
MH  - DNA Footprinting
MH  - DNA Probes/chemistry
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Gene Expression Regulation/genetics
MH  - Genes, Reporter/genetics
MH  - Genetic Vectors
MH  - Matrix Metalloproteinase 1
MH  - Matrix Metalloproteinase Inhibitors
MH  - Nuclear Proteins/metabolism/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-jun/metabolism/pharmacology
MH  - Rabbits
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Synovial Fluid/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription, Genetic/*drug effects
MH  - Transfection/genetics
MH  - Tretinoin/pharmacology
EDAT- 1996/11/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1002/(SICI)1097-4652(199611)169:2<320::AID-JCP11>3.0.CO;2-D [pii]
AID - 10.1002/(SICI)1097-4652(199611)169:2<320::AID-JCP11>3.0.CO;2-D [doi]
PST - ppublish
SO  - J Cell Physiol. 1996 Nov;169(2):320-32. doi: 
      10.1002/(SICI)1097-4652(199611)169:2<320::AID-JCP11>3.0.CO;2-D.