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Publication : FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase.

First Author  Adam-Klages S Year  1996
Journal  Cell Volume  86
Issue  6 Pages  937-47
PubMed ID  8808629 Mgi Jnum  J:35486
Mgi Id  MGI:82933 Doi  10.1016/s0092-8674(00)80169-5
Citation  Adam-Klages S, et al. (1996) FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase. Cell 86(6):937-47
abstractText  The initiation of intracellular signaling events through the 55 kDa tumor necrosis factor-receptor (TNF-R55) appears to depend on protein intermediates that interact with specific cytoplasmic domains of TNF-R55. By combined use of the yeast interaction trap system and a peptide scanning library, the novel WD-repeat protein FAN has been identified, which specifically binds to a cytoplasmic nine amino acid binding motif of TNF-R55. This region has been previously recognized as a distinct functional domain that is both required and sufficient for the activation of neutral sphingomyelinase (N-SMase). Overexpression of full-length FAN enhanced N-SMase activity in TNF-treated cells, while truncated mutants of FAN produced dominant negative effects. The data suggest that FAN regulates ceramide production by N-SMase, which is a crucial step in TNF signaling.
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