Abstract
Previous studies have indicated that ER-α can influence the activity of the MMP-13 promoter. ER-α activity is mediated by two separate transcriptional activation domains (AF-1 and AF-2). The present study focused on analyzing the roles of these domains on the activation of the MMP-13 promoter. Transfection of synoviocytes with an ER-α construct lacking the C-terminus AF-2 domain led to significant elevation in MMP-13 promoter activity compared to wild type ER-α. Progressive deletions in the N-terminal AF-1 domain led to significant losses in MMP-13 promoter activity. MMP-13 promoter mutagenesis indicated that an AP-1 regulatory site was essential for ER-α mutant activity. Thus, both AF-1 and AF-2 domains of ER-α are required for regulation of MMP-13 promoter activity. As ER variants and ER related proteins have been implicated in bone and joint disorders, these findings provide understanding of the possible role of ER variants in the development of such conditions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 211-220 |
| Number of pages | 10 |
| Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
| Volume | 1792 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2009 |
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Keywords
- AF-1
- AF-2
- AP-1 Site
- ER-α mutant
- Gene regulation
- MMP-13
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
Cite this
Distinct roles for AF-1 and -2 of ER-alpha in regulation of MMP-13 promoter activity. / Achari, Yamini; Lu, Ting; Katzenellenbogen, Benita S.; Hart, David A.
In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1792, No. 3, 01.03.2009, p. 211-220.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct roles for AF-1 and -2 of ER-alpha in regulation of MMP-13 promoter activity
AU - Achari, Yamini
AU - Lu, Ting
AU - Katzenellenbogen, Benita S.
AU - Hart, David A.
PY - 2009/3/1
Y1 - 2009/3/1
N2 - Previous studies have indicated that ER-α can influence the activity of the MMP-13 promoter. ER-α activity is mediated by two separate transcriptional activation domains (AF-1 and AF-2). The present study focused on analyzing the roles of these domains on the activation of the MMP-13 promoter. Transfection of synoviocytes with an ER-α construct lacking the C-terminus AF-2 domain led to significant elevation in MMP-13 promoter activity compared to wild type ER-α. Progressive deletions in the N-terminal AF-1 domain led to significant losses in MMP-13 promoter activity. MMP-13 promoter mutagenesis indicated that an AP-1 regulatory site was essential for ER-α mutant activity. Thus, both AF-1 and AF-2 domains of ER-α are required for regulation of MMP-13 promoter activity. As ER variants and ER related proteins have been implicated in bone and joint disorders, these findings provide understanding of the possible role of ER variants in the development of such conditions.
AB - Previous studies have indicated that ER-α can influence the activity of the MMP-13 promoter. ER-α activity is mediated by two separate transcriptional activation domains (AF-1 and AF-2). The present study focused on analyzing the roles of these domains on the activation of the MMP-13 promoter. Transfection of synoviocytes with an ER-α construct lacking the C-terminus AF-2 domain led to significant elevation in MMP-13 promoter activity compared to wild type ER-α. Progressive deletions in the N-terminal AF-1 domain led to significant losses in MMP-13 promoter activity. MMP-13 promoter mutagenesis indicated that an AP-1 regulatory site was essential for ER-α mutant activity. Thus, both AF-1 and AF-2 domains of ER-α are required for regulation of MMP-13 promoter activity. As ER variants and ER related proteins have been implicated in bone and joint disorders, these findings provide understanding of the possible role of ER variants in the development of such conditions.
KW - AF-1
KW - AF-2
KW - AP-1 Site
KW - ER-α mutant
KW - Gene regulation
KW - MMP-13
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U2 - 10.1016/j.bbadis.2009.01.002
DO - 10.1016/j.bbadis.2009.01.002
M3 - Article
C2 - 19185056
AN - SCOPUS:61349173907
VL - 1792
SP - 211
EP - 220
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 3
ER -