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Proposed model of LUBAC-mediated ubiquitination on cFLIP in the TNFα receptor signaling pathway. In normal conditions, linear ubiquitination of cFLIP induced by LUBAC inhibits Lys-48–linked ubiquitination of cFLIP, thereby suppressing caspase 8 activity and apoptosis process. When LUBAC is deficient, cFLIP cannot be ubiquitinated by LUBAC. Instead, cFLIP degrades through Lys-48–linked ubiquitination in a dependent manner, thereby promoting apoptosis process.
