Tumor necrosis factor receptor superfamily member 1A (TNFR1) (TNFR1)

Tumor necrosis factor receptor superfamily member 1A (TNFR1) is a ubiquitous membrane-bound receptor and key member of the TNF receptor superfamily that primarily binds TNF-α (and lymphotoxin-α), existing in both membrane and soluble forms. Upon ligand binding, TNFR1 trimerizes to initiate complex signaling cascades, recruiting adaptors like TRADD, RIP1, FADD, and TRAF2 to activate NF-κB for cell survival and pro-inflammatory gene expression, or to trigger caspase-8-dependent apoptosis via death domain interactions when survival signals fail. It also stimulates sphingomyelinase pathways generating ceramide for additional signaling in inflammation and anti-viral responses. Soluble TNFR1, generated by proteolytic shedding, acts as a decoy to neutralize excess TNF-α and dampen inflammation. Dysregulation underlies diseases like TRAPS (from mutations impairing clearance), multiple sclerosis susceptibility, and elevated serum levels in schizophrenia or dementia, while aberrant signaling contributes to cancer metastasis, fibrosis, and autoimmune inflammation. Though not directly targeted by small molecules, TNFR1 is therapeutically modulated via TNF inhibitors like etanercept, which prevent ligand binding but carry risks of immunosuppression.

Other names

Tumor necrosis factor receptor 1CD120ap55p60TNF-R1TNF-R55TNFR55p55-RTBP1FPFTNFAR

Ligand competition (TNF-α blockade preventing receptor trimerization and signaling), Receptor shedding modulation (proteolytic release of soluble TNFR1 to inhibit TNF-α)