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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
Author(s) -
Petrella Brenda L.,
Armstrong David A.,
Vincenti Matthew P.
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22693
Subject(s) - biology , microbiology and biotechnology , enhancer , gene knockdown , gene expression , kinase , mapk/erk pathway , regulation of gene expression , gene isoform , transcription factor , gene , genetics
Abstract 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. J. Cell. Physiol. 226: 3349–3354, 2011. © 2011 Wiley Periodicals, Inc.