TY - JOUR
T1 - The nuclear receptor corepressor SMRT inhibits interstitial collagenase (MMP-1) transcription through an HRE-independent mechanism
AU - Schroen, Daniel J.
AU - Don Chen, J.
AU - Vincenti, Matthew P.
AU - Brinckerhoff, Constance E.
N1 - Funding Information:
The authors wish to thank members of the Brinckerhoff and Chen laboratories for expert comments, suggestions and technical advice. This work was supported by a postdoctoral fellowship from the Arthritis Foundation (DJS), start-up funds from the Department of Pharmacology and Molecular Toxicology, an Institutional award from the American Cancer Society and a Howard Hughes pilot grant provided by the UMass Medical Center (JDC), NIH grants F32 AR08216 and K01 AR02024 (MPV), and grants from the NIH (AR-26599) and the RGK Foundation (Austin, TX) (CEB).
PY - 1997/8/8
Y1 - 1997/8/8
N2 - Nuclear receptors inhibit synthesis of collagenase 1 (matrix metalloproeinase-1; MMP-1), an enzyme that degrades interstitial collagens and contributes to joint pathology in rheumatoid arthritis. SMRT (Silencing Mediator for Retinoid and Thyroid hormone receptors) mediates the repressive effect of nuclear receptors at hormone responsive elements (HREs), prompting us to investigate whether this co-repressor could also regulate transcription of MMP-1, which lacks any known HREs. We find that primary synovial fibroblasts express SMRT. When over-expressed by transient transfection, SMRT inhibits MMP-1 promoter activity induced by interleukin-1 (IL-1), phorbol phorbol myristate acetate (PMA) or v-Src. SMRT apparently inhibits MMP-1 gene expression by interfering with one or more transcriptional elements clustered in a region between -321 and +63. We conclude that SMRT negatively regulates MMP-1 synthesis through a novel, HRE-independent mechanism that involves proximal regions of the MMP-1 promoter.
AB - Nuclear receptors inhibit synthesis of collagenase 1 (matrix metalloproeinase-1; MMP-1), an enzyme that degrades interstitial collagens and contributes to joint pathology in rheumatoid arthritis. SMRT (Silencing Mediator for Retinoid and Thyroid hormone receptors) mediates the repressive effect of nuclear receptors at hormone responsive elements (HREs), prompting us to investigate whether this co-repressor could also regulate transcription of MMP-1, which lacks any known HREs. We find that primary synovial fibroblasts express SMRT. When over-expressed by transient transfection, SMRT inhibits MMP-1 promoter activity induced by interleukin-1 (IL-1), phorbol phorbol myristate acetate (PMA) or v-Src. SMRT apparently inhibits MMP-1 gene expression by interfering with one or more transcriptional elements clustered in a region between -321 and +63. We conclude that SMRT negatively regulates MMP-1 synthesis through a novel, HRE-independent mechanism that involves proximal regions of the MMP-1 promoter.
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U2 - 10.1006/bbrc.1997.7073
DO - 10.1006/bbrc.1997.7073
M3 - Article
C2 - 9266828
AN - SCOPUS:0031559597
VL - 237
SP - 52
EP - 58
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -