Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

Interleukin-7 Regulates Adipose Tissue Mass and Insulin Sensitivity in High-Fat Diet-Fed Mice through Lymphocyte-Dependent and Independent Mechanisms

Although interleukin (IL)-7 is mostly known as a key regulator of lymphocyte homeostasis, we recently demonstrated that it also contributes to body weight regulation through a hypothalamic control. Previous studies have shown that IL-7 is produced by the human obese white adipose tissue (WAT) yet its potential role on WAT development and function in obesity remains unknown. Here, we first show that transgenic mice overexpressing IL-7 have reduced adipose tissue mass associated with glucose and insulin resistance. Moreover, in the high-fat diet (HFD)-induced obesity model, a single administration of IL-7 to C57BL/6 mice is sufficient to prevent HFD-induced WAT mass increase and glucose intolerance. This metabolic protective effect is accompanied by a significant decreased inflammation in WAT. In lymphocyte-deficient HFD-fed SCID mice, IL-7 injection still protects from WAT mass gain. However, IL-7-triggered resistance against WAT inflammation and glucose intolerance is lost in SCID mice. These results suggest that IL-7 regulates adipose tissue mass through a lymphocyte-independent mechanism while its protective role on glucose homeostasis would be relayed by immune cells that participate to WAT inflammation. Our observations establish a key role for IL-7 in the complex mechanisms by which immune mediators modulate metabolic functions

Etude de LMP1, oncogène majeur du virus d'Epstein-Barr (autorégulation de son expression par les effets antagonistes des voies de signalisation cellulaire JNK et NFkB)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Polysaccharide Microarrays: Application to the Identification of Heparan Sulphate Mimetics

International audienceThe interaction of polysaccharides with proteins modulates or triggers many biological effects. In particular, heparan sulphate proteoglycans (HSPGs) have multiple regulatory interactions with growth factors, enzymes, enzyme inhibitors, and some components of the extracellular matrix. The important role played by HSPGs has motivated the synthesis and selection of HSPG mimetics for modulating the biological activity of HS-binding proteins. We present hereinafter an efficient polysaccharide microarray method that allows the screening of HS-mimetic libraries towards HS-binding growth factors, a major class of polypeptides whose inhibition or potentiation is of high medical interest

The transition from elementary to secondary school: how does self-regulated learning strategy use evolves?

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Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling

International audienceThe GRB2 associated binder 1 (GAB1) is an essential docking/adaptor protein for transmitting intracellular signals of the MET tyrosine kinase receptor activated by hepatocyte growth factor/scatter factor (HGF/SF). We found that in response to hours of HGF/SF treatment, the GAB1 protein level is degraded by a mechanism involving MET activity and the proteasomal machinery. We also showed that GAB1 is both multi- and poly-ubiquitinated in a CBL-dependent manner. A long term exposure to HGF/SF caused a more sustained down-regulation of GAB1 than of MET, associated with a loss of reactivation of the ERK MAP kinases to subsequent acute ligand treatment. These data demonstrate that GAB1 is ubiquitinated by CBL and degraded by the proteasome, and plays a role in negative-feedback regulation of HGF/SF–MET signaling

Soybean response and profitability upon inoculation and nitrogen fertilisation in Belgium

The recent introduction of soybean cultivation in Belgium and several other north-western European countries holds great potential for sustainable agriculture. Agricultural practices must be fine-tuned to optimise yield and quality before soybean will become a profitable crop for Belgian farmers. The effect of inoculation and N fertilisation on crop yield, protein content and relative profitability of soybean in Belgium was studied. Trials with nitrogen (N) fertilisation and inoculation of soybean were performed during two seasons (2016 and 2017) at two locations (Geel and Merelbeke) in Belgium. Nitrogen was applied as mineral fertiliser at different doses (0 N, 35 N, 70 N or 140 N) at the day of sowing and/or at the R1 stage. Highest yields and protein contents were obtained upon inoculation, showing that inoculation is the most appropriate practice to increase yield and protein levels of soybean in Belgium. Inoculation also increased thousand grain weight and improved several biophysical parameters calculated from chlorophyll a fluorescence measurements. Additionally, inoculation and N fertilisation raised chlorophyll content of the soybean leaves and N content and N uptake of the aboveground biomass. Application of N inhibited nodulation of inoculated soybeans. Tolerance to lodging and oil contents were lower upon inoculation or N application. Relative profitability (RP) of inoculated soybeans was higher than for non inoculated soybeans. Application of N fertiliser to soybeans did not significantly increase RP. Optimisation of inoculation and nodulation is the best approach to maximise yield and protein content and thus to improve the economic viability of soybean cultivation for Belgian farmers in the short term

A novel dominant-negative mutant form of Epstein–Barr virus latent membrane protein-1 (LMP1) selectively and differentially impairs LMP1 and TNF signaling pathways

International audienc