Abstract
Post-translational modification by monoclonal nonspecific suppressor factor β (MNSFβ) has been involved in the regulation of a variety of cellular processes. Previous studies have demonstrated that MNSFβ covalently binds to the intracellular pro-apoptotic protein Bcl-G and regulates TLR-4-mediated signal transduction. Recently, we found that MNSFβ also covalently conjugates to endophilin II, a member of the endophilin A family, and inhibits the signal pathway upstream of IKK activation, but not downstream of TLR-2 signaling. In this study, we further examined the mechanism of action of MNSFβ in TLR-2-mediated signal transduction in macrophage-like cell line Raw264.7 cells. Although MNSFβ siRNA enhanced Pam3CDK4 (TLR-2-specific ligand)-stimulated TNFα production, Bcl-G siRNA did not affect. MNSFβ cDNA inhibited the Pam3CDK4-stimulated TNFα production. High-molecular weight (130 kDa) MNSFβ-adduct was induced in Pam3CDK4-stimulated Raw264.7 cells. This MNSFβ-adduct was not induced by LPS, indicative of the specificity of TLR-2-mediated signal transduction. Similar observations were seen in BALB/c peritoneal macrophages. Interestingly, 40-kDa MNSFβ-adduct was tyrosine phosphorylated by Pam3CDK4 stimulation. Collectively, novel MNSFβ-adducts may regulate TLR-2 signaling pathway in macrophages.
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Nakamura, M., Watanabe, J. & Watanabe, N. Ubiquitin-like protein MNSFβ regulates TLR-2-mediated signal transduction. Mol Cell Biochem 364, 39–43 (2012). https://doi.org/10.1007/s11010-011-1202-x
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DOI: https://doi.org/10.1007/s11010-011-1202-x