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Systems Biology of Death Receptor-Induced Apoptosis

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Systems Biology of Apoptosis

Abstract

Programmed cell death, termed apoptosis, plays a fundamental role in the development and homeostasis of multicellular organisms. Dysregulation of apoptosis can lead to numerous diseases, including autoimmune diseases, neurodegenerative diseases, and cancer. In mammalian cells apoptosis can be induced by intra- or extracellular stimuli. Extracellular stimuli comprise death ligands which lead to death receptor-induced apoptosis, referred to as extrinsic pathway. Intracellular signals, such as DNA damage, trigger the intrinsic pathway which results in the activation of Bcl-2 proteins and release of proapoptotic factors from the mitochondria into the cytosol. Apoptosis is executed by a family of cysteine proteases, the caspases, which eventually lead to the apoptotic phenotype, such as chromatin condensation, nuclear fragmentation, membrane blebbing, cell shrinkage, and formation of apoptotic bodies. The focus of this chapter is on understanding the signaling complexity of the extrinsic apoptotic pathway using systems biology. We summarize the main signaling paradigms and the major models of the extrinsic pathway. The development of these models has elucidated new insights into the regulation of apoptosis.

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Acknowledgments

We acknowledge the Helmholtz Alliance on Systems Biology (NW1SBCancer) and Helmholtz-Russia Joint Research Groups-2008-2 for supporting our work.

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Authors and Affiliations

  1. Division of Immunogenetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

    Kolja Schleich

  2. Bioquant, 69120, Heidelberg, Germany

    Kolja Schleich

  3. Department of Translational Inflammation Research, Institute of Experimental Internal Medicine, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

    Inna N. Lavrik

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Correspondence to Inna N. Lavrik .

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  1. Otto von Guericke University, Department of Translational Inflammation, Institute of Experimental Internal Medic, N/A, Magdeburg, 39120, Germany

    Inna N. Lavrik

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Schleich, K., Lavrik, I.N. (2012). Systems Biology of Death Receptor-Induced Apoptosis. In: Lavrik, I. (eds) Systems Biology of Apoptosis. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4009-3_2

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