Class II major histocompatibility complex transactivator (CIITA) inhibits matrix metalloproteinase-9 gene expression

被引:41
作者
Nozell, S [1 ]
Ma, ZD [1 ]
Wilson, C [1 ]
Shah, R [1 ]
Benveniste, EN [1 ]
机构
[1] Univ Alabama, Dept Cell Biol, Off Chair, Birmingham, AL 35294 USA
关键词
D O I
10.1074/jbc.M403738200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Matrix metalloproteinases ( MMPs) are a family of structurally related proteins with the collective capability to degrade all components of the extracellular matrix. Although MMP-mediated degradation of the extracellular matrix occurs physiologically, numerous pathological conditions exhibit increased MMP levels and excessive matrix degradation. Previous work from our laboratory has shown that interferon-gamma inhibits MMP-9 expression in a manner dependent upon STAT-1alpha. Here we extend our previous observations and show that the class II major histocompatibility complex transactivator (CIITA), a transcriptional target of STAT-1alpha, is also capable of inhibiting MMP-9 expression. By using stable cell lines that inducibly express CIITA or various mutant forms of CIITA, we show that CIITA requires the ability to bind the CREB-binding protein (CBP) to effectively inhibit MMP-9 expression. Furthermore, we show that CIITA-mediated inhibition of the MMP-9 gene does not rely on the transcriptional capability of CIITA. These findings support a model wherein CIITA inhibits MMP-9 expression by binding to and sequestering CBP, which reduces the levels of CBP at the MMP-9 promoter, inhibits levels of acetylated histone 3 at the MMP-9 promoter, and subsequently inhibits MMP-9 expression.
引用
收藏
页码:38577 / 38589
页数:13
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