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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 395, Issue 12


Principles and mechanisms of CD95 activation

Harald Wajant
  • Corresponding author
  • Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Röntgenring 11, D-97070 Würzburg, Germany
  • Email
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  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-09-16 | DOI: https://doi.org/10.1515/hsz-2014-0212


CD95 (Apo1/Fas) has been originally identified as the target of cell death-inducing antibodies. The recognition of CD95 as an apoptosis-triggering receptor represents one of the early milestones in the apoptosis field. Moreover, the research on CD95-induced cell death fostered various other discoveries of broad and general relevance in cell biology, for example, the identification of caspase 8 as the initiator caspase of the extrinsic apoptosis pathway. Activation of CD95-associated intracellular signaling pathways is not a simple consequence of ligand binding but is the fine-tuned result of a complex interplay of various molecular mechanisms that eventually determine the strength and quality of the CD95 response. There is growing evidence that different forms of CD95 stimulation trigger the assembly of CD95 signaling complexes of distinct composition. Moreover, the formation of signaling competent CD95 complexes is a multistep process and the subject of regulation by various cellular cues. This review addresses the relevance of the molecular nature of the CD95-stimulating agonist for the quality of the CD95 response and discusses the importance of modification, clustering, internalization, and lipid raft and actin association of CD95 for CD95 activity.

Keywords: acidic sphingomyelinase; apoptosis; caspase 8; CD95 (Apo1/Fas); CD95L; lipid rafts


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About the article

Harald Wajant

Harald Wajant is Professor at the Department of Internal Medicine II of the University Hospital Würzburg and head of the Division of Molecular Internal Medicine. He graduated in the Institute of Botany of the University of Stuttgart, Germany in 1993 and was then a postdoctoral research fellow and group leader at the Institute of Cell Biology and Immunology. Since 2003 he is Professor at the University Hospital Würzburg. His current research interests are the mechanisms of TNF receptor activation, apoptotic and non-apoptotic death receptor signaling and the development of antibodies and TNF ligand fusion proteins targeting TNF receptors.

Corresponding author: Harald Wajant, Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Röntgenring 11, D-97070 Würzburg, Germany, e-mail:

Received: 2014-06-13

Accepted: 2014-08-06

Published Online: 2014-09-16

Published in Print: 2014-12-01

Citation Information: Biological Chemistry, Volume 395, Issue 12, Pages 1401–1416, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0212.

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