IndraLab
Statements
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"Small interfering RNA (siRNA) against OTULIN resulted in anincrease in LUBAC induced NF-kappaB activation in HEK 293ET and U2OS cells and also in T-REx 293 cells stably expressing a doxycycline inducible OTULIN targeting microRNA (miRNA) (XREF_FIG A and XREF_FIG A-S6C)."
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"In contrast, depletion of OTULIN enhanced the activation of NF-kappaB in response to NOD2 stimulation 64."
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"Primary fibroblast cultures from this patient reveal a surprising phenotype of deregulated M1 linked Ub signalling, whereby OTULIN loss coincides with LUBAC downregulation to prevent intrinsic NF-kappaB activation."
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"Immune cell specific depletion of OTULIN leads to cell-type specific effects : constitutive active NF-kappaB signalling and overproduction of cytokines in myeloid cells, and down-regulation of linear ubiquitination signal in the B and T cells based on LUBAC degradation [XREF_BIBR]."
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"Mutation of Tyr56 in the OTULIN PIM domain abrogates HOIP binding, resulting in reduced ability of OTULIN to inhibit NF-kappaB activity and reduced cell death signaling [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"The recently identified linear-chain-specific DUB OTULIN has been implicated in the regulation of TNF induced NF-kappaB activation and cell death XREF_BIBR."
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"In contrast, OTULIN deficient myeloid cells are hyper-inflammatory and spontaneously activate NF-kappaB and secrete TNF."
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"OTULIN targets Met1-linked Ub and counteracts LUBAC auto-ubiquitination , thereby promoting NF-kappaB activation and MAPK signaling ."