p53 down-regulates matrix metalloproteinase-1 by targeting the communications between AP-1 and the basal transcription complex

Yubo Sun, Xiao Rong Zeng, Leonor Wenger, Gary S. Firestein, Herman S. Cheung

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We have previously reported that human matrix metalloproteinase-1 (MMP1) is a p53 target gene subject to down-regulation (Sun et al. [1999]: J Biol Chem 274:11535-11540). In the present study, we demonstrate that the down-regulation of the human -83MMP1 promoter fragment by p53 was abolished when the -72AP-1 site was eliminated and that a GAL4-cJun-mediated but not a GAL4-Elk1 -mediated induction of pFR-luci was effectively inhibited by p53 suggesting an AP-1 dependent but AP-1 binding independent mechanism. Results from gel mobility shift assays were consistent with an AP-I binding independent mechanism. We also demonstrate that both p300 and TATA box binding proteins cooperated with the transcription factor AP-1 to induce the promoter of MMP1; however, p53 only inhibited the p300-mediated induction of the MMP1 promoter and the inhibition was -72AP-1 dependent. Furthermore, the down-regulation of the MMP1 promoter and mRNA by p53 could be reversed by p300 and by a p53 binding p300 fragment that had no coactivator activity. Taken together, these results indicate that p53 down-regulates MMP1 mainly by disrupting the communications between the transactivator AP-1 and the basal transcriptional complex, which are partially mediated by p300. Finally, by using p53 truncated mutant constructs, we demonstrate that both the N-terminal activation domain and the C-terminal oligomerization domains of p53 were required for the down-regulation of MMP1 transcription.

Original languageEnglish (US)
Pages (from-to)258-269
Number of pages12
JournalJournal of cellular biochemistry
Volume92
Issue number2
DOIs
StatePublished - Dec 1 2004

Keywords

  • Coactivator protein p300
  • Matrix metalloproteinase-1
  • Transcription
  • Tumor suppressor protein p53

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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