FAN (factor associated with neutral sphingomyelinase activation), a moonlighting protein in TNF-R1 signaling.
TNF-α is a pleiotropic cytokine involved in the regulation of various biological effects, including cell survival and proliferation, cell differentiation, and cell death. Moreover, TNF-α triggers proinflammatory responses, essentially through its ability to promote the expression of various proinflammatory genes. Most of the biological effects initiated by TNF-α rely on its ability to bind to and activate TNF-R1. As a consequence, molecular complexes are being formed, resulting from the recruitment of multiple adaptor proteins to the intracellular TNF-R1 DD. The adaptor protein FAN constitutively binds to a proximal membrane domain of TNF-R1 called NSD. Herein, the role of FAN in TNF-α-induced cell signaling and biological responses is discussed.
Montfort
Anne
A
Institut de Médecine Moléculaire de Rangueil, Toulouse Cédex 4, France.
Martin
Pascal G P
PG
Levade
Thierry
T
Benoist
Hervé
H
Ségui
Bruno
B
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008970:Molecular Weight; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D013108:Sphingomyelin Phosphodiesterase