NF-kB binds to a polymorphic repressor element in the MMP-3 promoter

Ruth C. Borghaei; P. L. Rawlings Jr.; Masoud Javadi; J. Woloshin

NF-kB binds to a polymorphic repressor element in the MMP-3 promoter

Ruth C. Borghaei, P. L. Rawlings Jr., Masoud Javadi, J. Woloshin

Department of Bio-Medical Sciences (PCOM)

Research output: Contribution to journal › Article › peer-review

Abstract

A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kB in limiting the cytokine induced expression of MMP-3.

Original language	American English
Journal	Biochemical and biophysical research communications
Volume	316
State	Published - Jan 1 2004

Keywords

Gene expression regulation
NF-kB
Stromelysin-1
ZBP-89
binding protein
cytokine
immunoglobulin enhancer binding protein
interleukin 1
protein p50
stromelysin
synaptotagmin
unclassified drug
zinc binding protein 89
DNA binding protein
repressor protein
transcription factor
ZNF148 protein
human
allele
article
binding site
controlled study
fibroblast
gene activation
gene overexpression
genetic transcription
gingiva
human cell
hybrid
molecular cloning
priority journal
promoter region
protein expression
repressor gene
yeast
cytology
DNA responsive element
drug effect
enzyme repression
genetic polymorphism
genetics
metabolism
Binding Sites
DNA-Binding Proteins
Fibroblasts
Humans
Interleukin-1
Matrix Metalloproteinase 3
NF-kappa B
NF-kappa B p50 Subunit
Polymorphism
Genetic
Promoter Regions (Genetics)
Repressor Proteins
Response Elements
Transcription Factors

Disciplines

Genetics and Genomics

Cite this

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title = "NF-kB binds to a polymorphic repressor element in the MMP-3 promoter",

abstract = " A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kB in limiting the cytokine induced expression of MMP-3.",

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author = "Borghaei, {Ruth C.} and {Rawlings Jr.}, {P. L.} and Masoud Javadi and J. Woloshin",

year = "2004",

month = jan,

day = "1",

language = "American English",

volume = "316",

journal = "Biochemical and biophysical research communications",

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TY - JOUR

T1 - NF-kB binds to a polymorphic repressor element in the MMP-3 promoter

AU - Borghaei, Ruth C.

AU - Rawlings Jr., P. L.

AU - Javadi, Masoud

AU - Woloshin, J.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kB in limiting the cytokine induced expression of MMP-3.

AB - A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kB in limiting the cytokine induced expression of MMP-3.

KW - Gene expression regulation

KW - NF-kB

KW - Stromelysin-1

KW - ZBP-89

KW - binding protein

KW - cytokine

KW - immunoglobulin enhancer binding protein

KW - interleukin 1

KW - protein p50

KW - stromelysin

KW - synaptotagmin

KW - unclassified drug

KW - zinc binding protein 89

KW - DNA binding protein

KW - repressor protein

KW - transcription factor

KW - ZNF148 protein

KW - human

KW - allele

KW - article

KW - binding site

KW - controlled study

KW - fibroblast

KW - gene activation

KW - gene overexpression

KW - genetic transcription

KW - gingiva

KW - human cell

KW - hybrid

KW - molecular cloning

KW - priority journal

KW - promoter region

KW - protein expression

KW - repressor gene

KW - yeast

KW - cytology

KW - DNA responsive element

KW - drug effect

KW - enzyme repression

KW - genetic polymorphism

KW - genetics

KW - metabolism

KW - Binding Sites

KW - DNA-Binding Proteins

KW - Fibroblasts

KW - Humans

KW - Interleukin-1

KW - Matrix Metalloproteinase 3

KW - NF-kappa B

KW - NF-kappa B p50 Subunit

KW - Polymorphism

KW - Genetic

KW - Promoter Regions (Genetics)

KW - Repressor Proteins

KW - Response Elements

KW - Transcription Factors

UR - https://digitalcommons.pcom.edu/scholarly_papers/1222

M3 - Article

VL - 316

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

ER -

NF-kB binds to a polymorphic repressor element in the MMP-3 promoter

Abstract

Keywords

Disciplines

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Cite this