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pubmed-article:16621790pubmed:abstractTextMNSFbeta is a ubiquitously expressed member of the ubiquitin-like family that has been implicated in various biological functions. Previous studies have demonstrated that MNSFbeta covalently binds to intracellular proapoptotic protein Bcl-G in mitogen-activated murine T cells. In this study, we further investigated the intracellular mechanism of action of MNSFbeta in macrophage cell line, Raw 264.7 cells. We present evidence that MNSFbeta.Bcl-G complex associates with ERKs in non-stimulated Raw 264.7. We found that MNSFbeta.Bcl-G directly bound to ERKs and inhibited ERK activation by MEK1. In Raw 264.7 cells treated with MNSFbeta small interfering RNA (siRNA) lipopolysaccharide (LPS)-induced ERK1/2 activation was enhanced and LPS-induced JNK and p38 activation was unaffected. SiRNA-mediated knockdown of MNSFbeta increased tumor necrosis factor alpha (TNFalpha) expression at mRNA and protein levels in LPS-stimulated Raw 264.7 cells. Finally, we found that transfection with MNSFbeta expression construct resulted in a significant inhibition of LPS-induced ERK activation and TNFalpha production. Co-transfection experiments with MNSFbeta and Bcl-G greatly enhanced this inhibition. Collectively, these findings indicate that MNSFbeta might be implicated in the macrophage response to LPS.lld:pubmed
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pubmed-article:16621790pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:16621790pubmed:articleTitleThe ubiquitin-like protein MNSFbeta regulates ERK-MAPK cascade.lld:pubmed
pubmed-article:16621790pubmed:affiliationDepartment of Cooperative Medical Research, Collaboration Center, Faculty of Medicine, Shimane University, Izumo, Japan. nkmr0515@med.shimane-u.ac.jplld:pubmed
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