| First Author | Watanabe J | Year | 2013 |
| Journal | FEBS J | Volume | 280 |
| Issue | 5 | Pages | 1281-93 |
| PubMed ID | 23298187 | Mgi Jnum | J:201386 |
| Mgi Id | MGI:5513086 | Doi | 10.1111/febs.12120 |
| Citation | Watanabe J, et al. (2013) Ubiquitin-like protein MNSFbeta covalently binds to Bcl-G and enhances lipopolysaccharide/interferon gamma-induced apoptosis in macrophages. FEBS J 280(5):1281-93 |
| abstractText | Monoclonal non-specific suppressor factor beta (MNSFbeta) is a ubiquitously expressed member of the ubiquitin-like family that is involved in various biological functions. Previous studies have demonstrated that MNSFbeta covalently binds to intracellular pro-apoptotic protein Bcl-G and regulates the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) cascade in the mouse macrophage cell line Raw264.7. In this study, we demonstrate that MNSFbeta promotes lipopolysaccharide (LPS)/interferon gamma (IFNgamma)-induced apoptosis of Raw264.7 macrophages. In Raw264.7 cells treated with MNSFbeta small interfering RNA (siRNA), LPS/IFNgamma- or NO donor S-nitrosoglutathione-induced apoptosis was inhibited. siRNA-mediated knockdown of MNSFbeta did not affect inducible nitric-oxide synthase (iNOS) expression in LPS/IFNgamma-stimulated Raw264.7 cells. Conversely, co-transfection with MNSFbeta and Bcl-G greatly enhanced LPS/IFNgamma- induced apoptosis in Raw264.7 cells, accompanied by increased expression of p53 and decreased Cox-2 activity. Unlike co-transfection with wild-type MNSFbeta, co-transfection of a mutant MNSFbeta (G74A) and Bcl-G did not result in enhancement of LPS/IFNgamma-induced apoptosis. Co-over-expression of MNSFbeta and Bcl-G reduced S-nitrosoglutathione-induced ERK1/2 phosphorylation. Furthermore, electrophoretic mobility shift assay experiments revealed that MNSFbeta down-regulates the ERK/activator protein 1 (AP-1) signaling cascade which leads to Cox-2 activation. We also observed that MNSFbeta-Bcl-G promotes LPS/IFNgamma-induced apoptosis of mouse peritoneal macrophages, together with a decrease in Cox-2 expression. Taken together, our data indicate an apoptosis-enhancing effect of MNSFbeta-Bcl-G is due in part to down-regulation of Cox-2 activation in macrophages. |
