ESCRT proteins restrict constitutive NF-κB signaling by trafficking cytokine receptors

Article Article scientifique Article ESCRT proteins restrict constitutive NF-κB signaling by trafficking cytokine receptors eng 2016 author Mamińska Agnieszka author Bartosik Anna author Banach-Orłowska Magdalena author Pilecka Iwona 835758 author Jastrzębski Kamil author Zdżalik-Bielecka Daria author Castanon Ortega Irinka 664714 author Poulain Morgane author Neyen Claudine 910058 author Wolińska-Nizioł Lidia author Toruń Anna author Szymańska Ewelina author Kowalczyk Agata author Piwocka Katarzyna author Simonsen Anne author Stenmark Harald author Fürthauer Maximilian author Gonzalez Gaitan Marcos 645929 author Miaczynska Marta ra8 10.1126/scisignal.aad0848 1937-9145 https://stke.sciencemag.org/lookup/doi/10.1126/scisignal.aad0848 Because signaling mediated by the transcription factor nuclear factor κB (NF-κB) is initiated by ligands and receptors that can undergo internalization, we investigated how endocytic trafficking regulated this key physiological pathway. We depleted all of the ESCRT (endosomal sorting complexes required for transport) subunits, which mediate receptor trafficking and degradation, and found that the components Tsg101, Vps28, UBAP1, and CHMP4B were essential to restrict constitutive NF-κB signaling in human embryonic kidney 293 cells. In the absence of exogenous cytokines, depletion of these proteins led to the activation of both canonical and noncanonical NF-κB signaling, as well as the induction of NF-κB–dependent transcriptional responses in cultured human cells, zebrafish embryos, and fat bodies in flies. These effects depended on cytokine receptors, such as the lymphotoxin β receptor (LTβR) and tumor necrosis factor receptor 1 (TNFR1). Upon depletion of ESCRT subunits, both receptors became concentrated on and signaled from endosomes. Endosomal accumulation of LTβR induced its ligand-independent oligomerization and signaling through the adaptors TNFR-associated factor 2 (TRAF2) and TRAF3. These data suggest that ESCRTs constitutively control the distribution of cytokine receptors in their ligand-free state to restrict their signaling, which may represent a general mechanism to prevent spurious activation of NF-κB. Dewey 540 39 Département de biochimie 144 false Science Signaling 9 411 64ca889f-8044-42c8-a258-2b12b39dc1cb Article (Published version) Restricted ESCRT_MG_16.pdf 1972961 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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ESCRT proteins restrict constitutive NF-κB signaling by trafficking cytokine receptors	Science Signaling			2016	278	0

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Neyen, Claudine