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Many Checkpoints on the Road to Cell Death:Regulation of Fas–FasL Interactions and Fas Signaling in Peripheral Immune Responses

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Death Receptors and Cognate Ligands in Cancer

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 49))

Abstract

Interactions between the TNF-family receptor Fas (CD95) and Fas Ligand (FasL, CD178) can efficiently induce apoptosis and are critical for the maintenance of immunological self-tolerance. FasL is kept under strict control by transcriptional and posttranslational regulation. Surface FasL can be cleaved by metalloproteases, resulting in shed extracellular domains, and FasL can also traffic to secretory lysosomes. Each form of FasL has distinct biological functions. Fas is more ubiquitously expressed, but its apoptosis-inducing function is regulated by a number of mechanisms including submembrane localization, efficiency of receptor signaling complex assembly and activation, and bcl-2 family members in some circumstances. When apoptosis is not induced, Fas–FasL interactions can also trigger a number of activating and proinflammatory signals. Harnessing the apoptosis-inducing potential of Fas for therapy of cancer and autoimmune disease has been actively pursued, and despite a number of unexpected side-effects that result from manipulating Fas–FasL interactions, this remains a worthy goal.

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  1. Immunoregulation Unit, Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, USA, 20892

    Richard M. Siegel

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  1. Madhu Ramaswamy
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  2. Sophia Y. Clel
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  3. Anthony C. Cruz
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  4. Richard M. Siegel
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Correspondence to Richard M. Siegel .

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  1. Klinik für Allgemeine Chirurgie und, Universitätsklinikum Schleswig-Holstein, Arnold-Heller-Str. 7, Kiel, 24105, Germany

    Holger Kalthoff

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Ramaswamy, M., Clel, S., Cruz, A., Siegel, R. (2009). Many Checkpoints on the Road to Cell Death:Regulation of Fas–FasL Interactions and Fas Signaling in Peripheral Immune Responses. In: Kalthoff, H. (eds) Death Receptors and Cognate Ligands in Cancer. Results and Problems in Cell Differentiation, vol 49. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2008_24

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