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FasL-Independent Activation of Fas

  • Faustino Mollinedo
  • Consuelo Gajate
Chapter
Part of the Medical Intelligence Unit book series (MIUN)

Abstract

Fas death receptor (also named CD95 or APO-1) is physiologically activated through binding to its cognate ligand, FasL. Fas/FasL interaction induces oligomerization and aggregation of Fas receptor, leading eventually to apoptosis after protein-protein interactions with adaptor and effector proteins. However, recent evidences demonstrate that either oligomerization of the receptor in trimers, as well as Fas aggregation in large clusters do not require its interaction with FasL. Activation of Fas through its translocation into membrane rafts, forming Fas caps, can be rendered independently of FasL. This FasL-independent cocapping of Fas in membrane rafts generates high local concentrations of Fas, providing scaffolds for coupling adaptor and effector proteins involved in Fas signaling. Thus, Fas receptor can be modulated either extracellularly, via FasL, or intracellularly independently of its ligand. Unraveling the molecular mechanism involved in FasL-independent activation of Fas will raise putative novel therapeutic interventions, especially in disorders where apoptosis is deficient such as cancer and autoimmune diseases, avoiding in this way the deleterious side effects that preclude the use of systemic activation of the Fas receptor by its ligand.

Keywords

Death Domain Membrane Raft Death Effector Domain Antitumor Ether Lipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2006

Authors and Affiliations

  • Faustino Mollinedo
    • 1
  • Consuelo Gajate
    • 1
  1. 1.Centro de Investigacion del Cancer Instituto de Biologia Molecular y Celular del CancerCSIC-Universidad de SalamancaSalamancaSpain

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