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

Academic Article

Abstract

  • 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-γ inhibits MMP-9 expression in a manner dependent upon STAT-1α. Here we extend our previous observations and show that the class II major histocompatibility complex transactivator (CIITA), a transcriptional target of STAT-1α, 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.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Nozell S; Ma Z; Wilson C; Shah R; Benveniste EN
  • Start Page

  • 38577
  • End Page

  • 38589
  • Volume

  • 279
  • Issue

  • 37