当前位置： SCI文献检索 > ONCOGENE期刊下所有文献 > Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex.

Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex.

Abstract：

:Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and their combinations differentially regulate collagenase1 and stromelysin1 promoter activity. In transiently transfected cells, Ets2 activates both promoters whereas Erg induces collagenase1 but not stromelysin1 promoter activity. Moreover, Erg completely inhibits stromelysin1 promoter activation by Ets2. In gel shift assays however, the Erg protein bound little or not to the collagenase1 promoter, whereas it bound to the stromelysin1 promoter. By site-specific mutagenesis, we identified one major site at -88 that abolished collagenase1 promoter activation by Erg. Surprisingly, mutation of the collagenase1 AP1 site at -73 also abolished the activation by Erg suggesting that Erg cooperates with Fos/Jun in collagenase1 promoter regulation. Indeed, gel shift and in vitro protein interaction studies showed that Erg binds to the Fos/Jun complex. Thus, Erg represents the first example of a transcription factor that can distinguish between the collagenase1 and stromelysin1 promoters in that when Erg is recruited by Fos/Jun at the promoter, it transcriptionally activates collagenase1 gene but not stromelysin1 expression.

journal_name

Oncogene

journal_title

Oncogene

authors

Butticè G,Duterque-Coquillaud M,Basuyaux JP,Carrère S,Kurkinen M,Stéhelin D

subject

Has Abstract

pub_date

1996-12-05 00:00:00

pages

2297-306

issue

11

eissn

0950-9232

issn

1476-5594

journal_volume

13

pub_type

杂志文章

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