title: 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.
abstract: 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 naïve 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.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Han-Hyoung
authors.initials: HH
authors.lastname: Lee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.forename: Suk Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jihye
authors.initials: J
authors.lastname: Han
authors.forename: Joonbeom
authors.initials: J
authors.lastname: Bae
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Park
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Hwang
authors.forename: Taehoon
authors.initials: T
authors.lastname: Chun
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002467:Cell Nucleus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D000072000:NF-KappaB Inhibitor alpha; D010587:Phagocytosis; D021381:Protein Transport / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000276:immunology / Q000378:metabolism*; D058207:Sumoylation; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000276:immunology / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D018664:Interleukin-12