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CCAAT-enhancer-binding protein beta activation of MMP-1 gene expression in SW1353 cells: independent roles of extracellular signal-regulated and p90/ribosomal S6 kinases



CCAAT-enhancer-binding protein beta activation of MMP-1 gene expression in SW1353 cells: independent roles of extracellular signal-regulated and p90/ribosomal S6 kinases



Journal of Cellular Physiology 226(12): 3349-3354



CCAAT-enhancer-binding protein beta (CEBPB) is a pluripotent transcription factor that controls inflammation, proliferation, and differentiation. We recently reported a role for CEBPB during matrix metalloproteinase (MMP) gene expression, but the mechanisms involved are poorly understood. To address this we interrogated CEBPB-dependent MMP-1 and MMP-13 gene activation in the SW1353 chondrosarcoma cell line, a well-established model of MMP gene regulation in mesenchymal cells. IL-1B treatment increased CEBPB expression in SW1353 cells over a 24-h period and knockdown of CEBPB with shRNA abrogated IL-1B-dependent MMP-1 and MMP-13 gene activation. Exogenous expression of the CEBPB isoforms LAP1 or LAP2 was sufficient to induce MMP-1 mRNA levels comparable to IL-1B-induced expression, while the truncated LIP isoform repressed IL-1B-induced MMP-1. Although exogenous CEBPB expression induced MMP-13 mRNA, the response was less robust than was observed for MMP-1. CEBPB is activated by the extracellular-regulated kinases (ERK) and RSK kinases in response to oncogenes and growth factors. We found that the MEK inhibitor U0126 and the RSK inhibitor BI-D1870 both reduced IL-1B-dependent MMP-1 gene expression in SW1353 cells. Although ERK is known to phosphorylate CEBPB on threonine 235, this residue was not required for CEBPB-dependent activation of MMP-1. In contrast, the RSK target serine 321 was required for LAP1 and LAP2-dependent activation of MMP-1. These findings establish CEBPB as a critical intermediate for IL-1B-dependent MMP gene activation and assign specific roles for the ERK and RSK kinases in this pathway.

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Accession: 051887339

Download citation: RISBibTeXText

PMID: 21344389

DOI: 10.1002/jcp.22693


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