necrosome
The necrosome is a cytosolic protein complex that mediates necroptosis, a regulated form of necrotic cell death. The core components are receptor-interacting protein kinase 1 (RIPK1) and RIPK3, which interact through RHIM domains; in many models, mixed lineage kinase domain-like protein (MLKL) is recruited and phosphorylated by RIPK3 to execute necroptosis. Necrosome formation is favored when tumor necrosis factor (TNF) signaling occurs and caspase-8 activity is inhibited or absent, shifting the cell death program from apoptosis to necroptosis.
In canonical TNF signaling, RIPK1 is recruited to complex I at the TNF receptor and becomes ubiquitinated,
Regulation of the necrosome involves ubiquitination, deubiquitination, phosphorylation, and proteasomal degradation. Inhibitors such as necrostatin-1 target