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Nonapoptotic functions of Fas/ CD 95 in the immune response
Author(s) -
Guégan JeanPhilippe,
Legembre Patrick
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14292
Subject(s) - fas receptor , fas ligand , immune system , tumor necrosis factor alpha , receptor , transmembrane protein , biology , microbiology and biotechnology , signal transduction , apoptosis , inflammation , cancer research , immunology , programmed cell death , biochemistry
CD 95 (also known as Fas) is a member of the tumor necrosis factor receptor ( TNFR ) superfamily. Its cognate ligand, CD 95L, is implicated in immune homeostasis and immune surveillance. Mutations in this receptor are associated with a loss of apoptotic signaling and have been detected in an autoimmune disorder called autoimmune lymphoproliferative syndrome ( ALPS ) type Ia, which shares some clinical features with systemic lupus erythematosus ( SLE ). In addition, deletions and mutations of CD 95 have been described in many cancers, which led researchers to initially classify this receptor as a tumor suppressor. More recent data demonstrate that CD 95 engagement evokes nonapoptotic signals that promote inflammation and carcinogenesis. Transmembrane CD 95L (m‐ CD 95L) can be cleaved by metalloproteases, releasing a soluble ligand (s‐ CD 95L). Soluble and membrane‐bound CD 95L show different stoichiometry (homotrimer versus multimer of homotrimers, respectively), which differentially affects CD 95‐mediated signaling through molecular mechanisms that remain to be elucidated. This review discusses the biological roles of CD 95 in light of recent experiments addressing how a death receptor can trigger both apoptotic and nonapoptotic signaling pathways.