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 and Brunner, Thomas

ISSN:

0006-4971

ISBN:

16332972

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 May 2014 23:13

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)

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