YB-1 binds to the MMP-13 promoter sequence and represses MMP-13 transactivation via the AP-1 site

Abstract

Matrix metalloproteinases (MMPs) are key enzymes that implement degradation of the extracellular matrix during cellular invasion in development, tissue remodeling, and pathogenic disease states. MMP-13 has pivotal roles in the pathogenesis of invasive cancers and arthritis. Here we report the identification of Y-box binding protein-1 (YB-1) as a new repressor of MMP-13 transactivation. YB-1 binds in vitro in DNA affinity chromatography to the activator protein-1 (AP-1) DNA sequence within the MMP-13 promoter. Chromatin immunoprecipitation assays reveal that YB-1 binds in living cells to the MMP-13 gene promoter, to a region of the MMP-13 promoter containing the AP-1 site. YB-1 represses tumor promoter-induced MMP-13 promoter transactivation at the AP-1 site. This is the first report demonstrating YB-1 binding in vitro and in living cells to a mammalian AP-1 target gene, and the first report of YB-1 regulation of the MMP-13 promoter. KeywordsActivator protein-1 (AP-1); chromatin immunoprecipitation (ChIP); matrix metalloproteinase-13 (MMP-13); NAPSTER; transactivation; Y-box binding protein-1 (YB-1)

Sumoylation and Nuclear Translocation of S100A4 Regulate IL-1β-mediated Production of Matrix Metalloproteinase-13

“…The transcription factor Runt domain factor-2 (Runx-2) binds at a unique site on the MMP-13 promoter, and also interacts with AP-1 to mediate MMP-13 transcription (49,50). Recently, YB-1, a member of the Y-box family of DNA-binding proteins, was shown to directly bind at the AP-1 site on MMP-13 and regulate its transcription (51). Thus, the AP-1 binding site on the promoter region of the MMP-13 gene plays a critical role in MMP-13 gene expression.…”

The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis

“…Raffetseder et al (2009) reported that YB1 could upregulate chemokine ligand 5 (CCL5) transcription in monocytes, while repressing CCL5 transcription in differentiated macrophages. YB1 repression of matrix metalloproteinase-13 (MMP-13) expression through binding of the adaptor protein-1 (AP-1) site of the MMP-13 promoter has also been demonstrated, and MMP-13 repression by YB1 can play a pivotal role in the pathogenesis of invasive cancers and arthritis (Samuel et al, 2007). Furthermore, Evdokimova et al (2009) demonstrated that YB1 protein level elevation is associated with reduced proliferation rates in disseminated mesenchymal-like breast carcinoma cells.…”

“…YB1 can recognize and bind specific promoter sequences containing the 5¢-CTGATTGG-3¢ motif (the so-called Y-box motif) through its CSD domain and can both positively and negatively regulate the expression of a large number of genes involved in proliferation and differentiation (Kosnopfel et al, 2014). YB1 was subsequently found to bind other DNA sequences, such as AP-1 binding sites (Samuel et al, 2007) and single-stranded DNA (ss-DNA) sequences (C/T-or GC/GA-rich sequences) (Izumi et al, 2001;Zasedateleva et al, 2002). Two of our recent studies have demonstrated YB1 interaction through its C-terminal domain (CTD) with a GGGCGG motif (known as a GC-box) in the promoters of proliferation and differentiation-related genes in vascular smooth muscle cells (VSMCs).…”

ANKRD1 Acts as a Transcriptional Repressor of MMP13 via the AP-1 Site

“…ANKRD1 interaction with the nuclear factor YB-1 at a hypoxia-inducible factor 1 site in the myosin light-chain 2v (MLC 2v) promoter negatively regulates myosin expression (10). YB-1 has also been shown to interact with the AP-1 site within the MMP-13 promoter, and its overexpression potently represses AP-1-dependent transactivation (49). Interestingly, nucleolin and YB-1 interact with each other, and both proteins bind to RNA to form a complex (50).…”