Transition from TNF-Induced Inflammation to Death Signaling

Tumor necrosis factor (TNF) plays a key role in inflammatory responses and in various cellular events such as apoptosis and necroptosis. The interaction of TNF with its receptor, TNFR1, drives the initiation of complex molecular pathways leading to inflammation and cell death. RARγ is released from the nucleus to orchestrate the formation of the cytosolic death complexes, and it is cytosolic RARγ that plays a pivotal role in switching TNF-induced inflammatory responses to RIPK1-initiated cell death. Thus, RARγ provides a checkpoint for the transition from inflammatory signaling to death machinery of RIPK1-initiated cell death in response to TNF. Here, we use techniques to identify RARγ as a downstream mediator of TNFR1 signaling complex. We use confocal imaging to show the localization of RARγ upon activation of cell death. Immunoprecipitation of RARγ identified the interacting proteins.