Identification of a novel cell death checkpoint in the TNF signalling pathway
Flanders Institute for Biotechnology (VIB) News Sep 29, 2017
Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a very important role in orchestrating the immune response. Nevertheless, inappropriate signalling by TNF can also be detrimental and implicated in a variety of human inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. The pathogenic role of TNF in inflammatory conditions has long been thought to result from the ability of TNF to induce expression of a wide panel of proinflammatory mediators, but more recent studies have demonstrated that binding of TNF to its cognate receptor also promotes inflammation by inducing cell death, in the form of apoptosis and necrosis. Interfering with cell death induction therefore emerges as a promising therapeutic approach for the treatment of inflammatory conditions.
The research team of Prof. Bertrand (VIB-UGent), in the unit headed by Prof. Vandenabeele, is investigating the molecular mechanisms that protect the cells from death, and which are dysregulated in pathologic conditions. In the journal Nature Cell Biology, the group of Prof. Bertrand revealed the existence of a new cell death checkpoint in the TNF pathway. Dondelinger, Delanghe and colleagues show that MK2 protects the cells from death by inactivating the kinase RIPK1 through phosphorylation. Importantly, they show that this protective mechanism is affected in some inflammatory conditions and consequently results in cell death. This cell death can however be completely prevented by pharmacological inhibition of RIPK1. Together with other studies, this work highlights the promising therapeutic potential of RIPK1 kinase inhibitor for the treatment of inflammatory diseases.
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The research team of Prof. Bertrand (VIB-UGent), in the unit headed by Prof. Vandenabeele, is investigating the molecular mechanisms that protect the cells from death, and which are dysregulated in pathologic conditions. In the journal Nature Cell Biology, the group of Prof. Bertrand revealed the existence of a new cell death checkpoint in the TNF pathway. Dondelinger, Delanghe and colleagues show that MK2 protects the cells from death by inactivating the kinase RIPK1 through phosphorylation. Importantly, they show that this protective mechanism is affected in some inflammatory conditions and consequently results in cell death. This cell death can however be completely prevented by pharmacological inhibition of RIPK1. Together with other studies, this work highlights the promising therapeutic potential of RIPK1 kinase inhibitor for the treatment of inflammatory diseases.
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