The mouse small ubiquitin-like modifier-2 (SUMO-2) inhibits interleukin-12 (IL-12) production in mature dendritic cells by blocking the translocation of the p65 subunit of NFκB into the nucleus.

Post-translational modification by small ubiquitin-like modifier (SUMO) is involved in several significant cellular events. In particular, SUMO-1 and SUMO-4 modifications of IκBα have been shown to be actively involved in NFκB regulation. However, among the SUMO family, the specific function of SUMO-2/3 remains relatively unknown. In addition, it is not ...
clear whether SUMO-2/3 follows the same functional role as SUMO-1 and SUMO-4 during the activation of NFκB. In this study, we examined the influence of mouse SUMO-2 during the maturation of dendritic cells (DCs). Our results showed that the ectopic expression of SUMO-2 does not affect the cell surface expression of MHC class II molecule (A(b)) and co-stimulatory molecules (CD80 and CD86), and the efficiency of antigen uptake. However, the ectopic expression of mouse SUMO-2 inhibited IL-12 secretion by blocking the translocation of the p65 subunit of NFκB into the nucleus, which led to the polarization of naive CD4(+) T cells to T helper 2 (Th2) shift in vitro. Further analyses showed that SUMO-2 directly modified IκBα. These results indicate that the functional role of SUMO-2/3 in the regulation of NFκB activity was conserved during evolution.
Mesh Terms:
Animals, Antigen Presentation, Blotting, Western, Cell Differentiation, Cell Nucleus, Cell Separation, Chromatin Immunoprecipitation, Dendritic Cells, Electrophoretic Mobility Shift Assay, Flow Cytometry, I-kappa B Proteins, Interleukin-12, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Phagocytosis, Protein Transport, Reverse Transcriptase Polymerase Chain Reaction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Th2 Cells, Transcription Factor RelA
Mol. Immunol.
Date: Sep. 01, 2011
127714
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