MTA1 Coregulation of Transglutaminase 2 Expression and Function during Inflammatory Response

作者：Ghanta Krishna Sumanth; Pakala Suresh B; Reddy Sirigiri Divijendra Natha; Li Da Qiang; Nair Sujit S; Kumar Rakesh^*

来源：Journal of Biological Chemistry, 2011, 286(9): 7132-7138.

DOI：10.1074/jbc.M110.199273

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-kappa B 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-kappa B 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-kappa B 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-kappa B signaling in stimulated macrophages.

• 出版日期2011-3-4