MTA1 coregulation of transglutaminase 2 expression and function during inflammatory response.

Although both metastatic tumor antigen 1 (MTA1), a master chromatin modifier, and transglutaminase 2 (TG2), a multifunctional enzyme, are known to be activated during inflammation, it remains unknown whether these molecules regulate inflammatory response in a coordinated manner. Here we investigated the role of MTA1 in the regulation of TG2 ...
expression in bacterial lipopolysaccharide (LPS)-stimulated mammalian cells. While studying the impact of MTA1 status on global gene expression, we unexpectedly discovered that MTA1 depletion impairs the basal as well as the LPS-induced expression of TG2 in multiple experimental systems. We found that TG2 is a chromatin target of MTA1 and of NF-κB signaling in LPS-stimulated cells. In addition, LPS-mediated stimulation of TG2 expression is accompanied by the enhanced recruitment of MTA1, p65RelA, and RNA polymerase II to the NF-κB consensus sites in the TG2 promoter. Interestingly, both the recruitment of p65 and TG2 expression are effectively blocked by a pharmacological inhibitor of the NF-κB pathway. These findings reveal an obligatory coregulatory role of MTA1 in the regulation of TG2 expression and of the MTA1-TG2 pathway, at least in part, in LPS modulation of the NF-κB signaling in stimulated macrophages.
Mesh Terms:
Animals, Breast Neoplasms, Cell Line, Tumor, Chromatin Immunoprecipitation, Female, Fibroblasts, GTP-Binding Proteins, Gene Expression Regulation, Enzymologic, Histone Deacetylases, Humans, Inflammation, Lipopolysaccharides, Macrophages, Peritoneal, Mice, NF-kappa B, Repressor Proteins, Transcription Factors, Transglutaminases
J. Biol. Chem.
Date: Mar. 04, 2011
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