Tumor necrosis factor receptor-associated factor 1 (TRAF1)

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF protein family, acting as an adaptor and signaling molecule in immune and inflammatory pathways. Unlike most other TRAF proteins, TRAF1 lacks a N-terminal RING finger domain, distinguishing its structural and functional properties. TRAF1 is best known for forming heterodimers with TRAF2, which are required for TNF-alpha–mediated activation of the MAPK8/JNK and NF-κB pathways; these are critical regulators of inflammation, cell survival, and apoptosis. TRAF1 also interacts with several other proteins, including the IAP family (affecting anti-apoptotic signaling), CD40, and TANK. TRAF1 serves as a regulator—sometimes positive, sometimes negative—of immune system activation and has a suppressive role in certain inflammatory cascades by interfering with NEMO ubiquitination downstream of toll-like receptor signaling. TRAF1 has been implicated in inflammatory and autoimmune conditions, certain cancers, and immune responses to viral infections, but no drugs have yet been developed targeting it directly.

Other names

TRAF1EBI6TNF receptor associated factor 1MGC:10353

Drugs targeting TRAF1-associated pathways generally act by modulating NF-κB or JNK signaling, inhibiting pro-inflammatory cytokine signaling, or promoting apoptosis via TNF receptor modulation. Direct TRAF1 targeting (as a therapeutic mechanism) is currently under investigation.