  Induction of the Alternative NF-{kappa}B Pathway by Lymphotoxin {alpha}{beta} (LT{alpha}{beta}) Relies on Internalization of LT{beta} Receptor; Remouchamps, Caroline  ; et alin Molecular & Cellular Biology (2011), 21 Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still ... [more ▼] Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB. [less ▲] Detailed reference viewed: 45 (13 ULg) Biology and Signal Transduction pathways of the Lymphotoxin-αβ/LTβR systemRemouchamps, Caroline ; ; et alin Cytokine & Growth Factor Reviews (2011), 22 This review focuses on the biological functions and signalling pathways activated by Lymphotoxin α (LTα)/Lymphotoxin β (LTβ) and their receptor LTβR. Genetic mouse models shed light on crucial roles for ... [more ▼] This review focuses on the biological functions and signalling pathways activated by Lymphotoxin α (LTα)/Lymphotoxin β (LTβ) and their receptor LTβR. Genetic mouse models shed light on crucial roles for LT/LTβR to build and to maintain the architecture of lymphoid organs and to ensure an adapted immune response against invading pathogens. However, chronic inflammation, autoimmunity, cell death or cancer development are disorders that occur when the LT/LTβR system is twisted. Biological inhibitors, such as antagonist antibodies or decoy receptors, have been developed and used in clinical trials for diseases associated to the LT/LTβR system. Recent progress in the understanding of cellular trafficking and NF-κB signaling pathways downstream of LTα/LTβ may bring new opportunities to develop therapeutics that target the pathological functions of these cytokines. [less ▲] Detailed reference viewed: 52 (26 ULg)The hidden function of NIK (NF-κB-Inducing Kinase) in cell death; ; Remouchamps, Caroline et alConference (2011) Detailed reference viewed: 21 (5 ULg)TNFL–Induced p100 processing (TIPP) relies on the internalization of the cognate TNFR; ; Remouchamps, Caroline et alConference (2010, January) Detailed reference viewed: 3 (1 ULg) |
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