NDLI: Posttranslational regulation of Fas ligand function

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Posttranslational regulation of Fas ligand function

Content Provider	Springer Nature : BioMed Central
Author	Voss, Matthias Lettau, Marcus Paulsen, Maren Janssen, Ottmar
Abstract	The TNF superfamily member Fas ligand acts as a prototypic death factor. Due to its ability to induce apoptosis in Fas (APO-1, CD95) expressing cells, Fas ligand participates in essential effector functions of the immune system. It is involved in natural killer cell- and T cell-mediated cytotoxicity, the establishment of immune privilege, and in termination of immune responses by induction of activation-induced cell death. In addition, Fas ligand-positive tumours may evade immune surveillance by killing Fas-positive tumour-infiltrating cells. Given these strong cytotoxic capabilities of Fas ligand, it is obvious that its function has to be strictly regulated to avoid uncontrolled damage. In hematopoietic cells, the death factor is stored in secretory lysosomes and is mobilised to the immunological synapse only upon activation. The selective sorting to and the release from this specific lysosomal compartment requires interactions of the Fas ligand cytosolic moiety, which mediates binding to various adapter proteins involved in trafficking and cytoskeletal reorganisation. In addition, Fas ligand surface expression is further regulated by posttranslational ectodomain shedding and subsequent regulated intramembrane proteolysis, releasing a soluble ectodomain cytokine into the extracellular space and an N-terminal fragment with a potential role in intracellular signalling processes. Moreover, other posttranslational modifications of the cytosolic domain, including phosphorylation and ubiquitylation, have been described to affect various aspects of Fas ligand biology. Since FasL is regarded as a potential target for immunotherapy, the further characterisation of its biological regulation and function will be of great importance for the development and evaluation of future therapeutic strategies.
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/1478-811X-6-11.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/1478-811X-6-11
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	6
Language	English
Publisher	BioMed Central
Publisher Date	2008-12-29
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Lipid Raft FasL Expression Secretory Lysosome Tumour Necrosis Factor Ligand Hematopoietic Progenitor Kinase
Content Type	Text
Resource Type	Review
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

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