Posttranscriptional regulation of Fas (CD95) ligand killing activity by lipid rafts

Nachbur, Ueli; Kassahn, Daniela; Yousefi, Shida; Legler, Daniel F; Brunner, Thomas (2006). Posttranscriptional regulation of Fas (CD95) ligand killing activity by lipid rafts. Blood, 107(7), pp. 2790-6. Washington, D.C.: American Society of Hematology 10.1182/blood-2005-07-2744

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Fas (CD95/Apo-1) ligand-mediated apoptosis induction of target cells is one of the major effector mechanisms by which cytotoxic lymphocytes (T cells and natural killer cells) kill their target cells. In T cells, Fas ligand expression is tightly regulated at a transcriptional level through the activation of a distinct set of transcription factors. Increasing evidence, however, supports an important role for posttranscriptional regulation of Fas ligand expression and activity. Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains, critically involved in the regulation of membrane receptor signaling complexes through the clustering and concentration of signaling molecules. Here, we now provide evidence that Fas ligand is constitutively localized in lipid rafts of FasL transfectants and primary T cells. Importantly, disruption of lipid rafts strongly reduces the apoptosis-inducing activity of Fas ligand. Localization to lipid rafts appears to be predominantly mediated by the characteristic cytoplasmic proline-rich domain of Fas ligand because mutations of this domain result in reduced recruitment to lipid rafts and attenuated Fas ligand killing activity. We conclude that Fas ligand clustering in lipid rafts represents an important control mechanism in the regulation of T cell-mediated cytotoxicity.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology 04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Yousefi, Shida, Brunner, Thomas (A)
ISSN:	0006-4971
ISBN:	16332972
Publisher:	American Society of Hematology
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	29 Mar 2023 23:32
Publisher DOI:	10.1182/blood-2005-07-2744
PubMed ID:	16332972
Web of Science ID:	000236656900040
URI:	https://boris.unibe.ch/id/eprint/18758 (FactScience: 996)