Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes

Panda, Swarupa; Nilsson, Jonas A.; Gekara, Nelson O.

doi:10.1016/j.immuni.2015.09.010

Cited by 76 publications

(100 citation statements)

References 38 publications

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“…)22, and innate immunity(Panda et al . )23. In the current study, there were far higher levels of TRAF6, IL-1β, IL-6, IL-8, and IL-33 in the debris group, demonstrating TRAF6 plays a key role in the process of aseptic inflammatory loosening.…”

Section: Discussionsupporting

confidence: 44%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured. Results indicated that FBXL2-mediated TRAF6 ubiquitination and degradation also plays an important role in aseptic periprosthetic loosening process, and LIPUS prevents such loosening by strengthening this pathway.

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Section: Discussionsupporting

confidence: 44%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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“…40 The present study revealed that Mysm1 is required for expression of IRF2 and IRF8 in preserving self-renewal of HSC 23, 24, 25 and in governing lineage commitment of HSC. 26, 27 IRF2 functions as a suppressor of IFN-I signaling by occupying the IRF consensus site on target genes and subsequently preventing DNA binding by IRF1, 41 which has an important role in maintaining quiescent HSC pool.…”

Section: Discussionmentioning

confidence: 53%

Mysm1 is required for interferon regulatory factor expression in maintaining HSC quiescence and thymocyte development

et al. 2016

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Mysm1−/− mice have severely decreased cellularity in hematopoietic organs. We previously revealed that Mysm1 knockout impairs self-renewal and lineage reconstitution of HSCs by abolishing the recruitment of key transcriptional factors to the Gfi-1 locus, an intrinsic regulator of HSC function. The present study further defines a large LSKs in >8-week-old Mysm1−/− mice that exhibit increased proliferation and reduced cell lineage differentiation compared with those of WT LSKs. We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1−/− HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis. We further found that the lower expressions of IRF2 and IRF8 led to an enhanced transcription of p53 in Mysm1−/− HSCs, which was recently defined to have an important role in mediating Mysm1−/−-associated defects. The study also revealed that Mysm1−/− thymocytes exhibited lower IRF2 expression, but had higher Sca1 expression, which has a role in mediating thymocyte death. Furthermore, we found that the thymocytes from B16 melanoma-bearing mice, which display severe thymus atrophy at late tumor stages, exhibited reduced Mysm1 and IRF2 expression but enhanced Sca1 expression, suggesting that tumors may downregulate Mysm1 and IRF2 for thymic T-cell elimination.

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“…In response to PRR triggering, TRAF6 and TRAF3 undergo K63-linked polyubiquitinaton, enabling these molecules to act as scaffolds for the recruitment and subsequent proximity-dependent activation of "downstream" signalling molecules (Hacker et al, 2006;Panda et al, 2015). TRAF6 and TRAF3 are critical points of convergence for many PRR pathways that control the transcriptional induction of innate immune mediators.…”

Section: Lvs Blocks Proximal Polyubiquitination and Phosphorylationmentioning

confidence: 99%

“…Immunoprecipitation and immunoblot analyses were performed as detailed in our recent study (Panda et al, 2015). Immunoprecipitation and immunoblot analyses were performed as detailed in our recent study (Panda et al, 2015).…”

Section: Infection Of Bone Marrow-derived Macrophagesmentioning

confidence: 99%

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Subversion of innate immune responses byFrancisellainvolves the disruption of TRAF3 and TRAF6 signalling complexes

Putzová

Panda

Härtlová

et al. 2017

Cellular Microbiology

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The success of pathogens depends on their ability to circumvent immune defences. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here, we show that Francisella triggers but concomitantly inhibits the Toll-like receptor, RIG-I-like receptor, and cytoplasmic DNA pathways. Francisella subverts these pathways at least in part by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of pattern recognition receptors. We show that this mode of inhibition requires a functional type VI secretion system and/or the presence of live bacteria in the cytoplasm. The ability of Francisella to enter the cytosol while simultaneously inhibiting multiple pattern recognition receptor pathways may account for the notable capacity of this bacterium to invade and proliferate in the host without evoking a self-limiting innate immune response.

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Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes

Cited by 76 publications

References 38 publications

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Mysm1 is required for interferon regulatory factor expression in maintaining HSC quiescence and thymocyte development

Subversion of innate immune responses byFrancisellainvolves the disruption of TRAF3 and TRAF6 signalling complexes

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