CD95-mediated cell signaling in cancer: mutations and post-translational modulations

Apoptosis has emerged as a fundamental process important in tissue homeostasis, immune response, and during development. CD95 (also known as Fas), a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been initially cloned as a death receptor. Its cognate ligand, CD95L, is mainly f...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2012-04, Vol.69 (8), p.1261-1277
Main Authors: Tauzin, Sébastien, Debure, Laure, Moreau, Jean-François, Legembre, Patrick
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Base Sequence
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cancer
Cell Biology
fas Receptor - chemistry
fas Receptor - genetics
fas Receptor - immunology
fas Receptor - metabolism
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Life Sciences
Lipids
Molecular biology
Molecular Sequence Data
Mutation
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Protein Processing, Post-Translational
Review
Signal Transduction
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Summary:Apoptosis has emerged as a fundamental process important in tissue homeostasis, immune response, and during development. CD95 (also known as Fas), a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been initially cloned as a death receptor. Its cognate ligand, CD95L, is mainly found at the plasma membrane of activated T-lymphocytes and natural killer cells where it contributes to the elimination of transformed and infected cells. According to its implication in the immune homeostasis and immune surveillance, and since several malignant cells of various histological origins exhibit loss-of-function mutations, which cause resistance towards the CD95-mediated apoptotic signal, CD95 has been classified as a tumor suppressor gene. Nevertheless, this assumption has been recently challenged, as in certain pathophysiological contexts, CD95 engagement transmits non-apoptotic signals that promote inflammation, carcinogenesis or liver/peripheral nerve regeneration. The focus of this review is to discuss these apparent contradictions of the known function(s) of CD95.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-011-0866-4