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Cell death controlling complexes and their potential therapeutic role

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Abstract

Programmed cell death plays a central role in the regulation of homeostasis and development of multicellular organisms. Deregulation of programmed cell death is connected to a number of disorders, including cancer and autoimmune diseases. Initiation of cell death occurs in the multiprotein complexes or high molecular weight platforms. Composition, structure, and molecular interactions within these platforms influence the cellular decision toward life or death and, therefore, define the induction of a particular cell death program. Here, we discuss in detail the key cell-death complexes—including DISC, complex II, and TNFRI complex I/II, and the necrosome, RIPoptosome, apoptosome, and PIDDosome—that control apoptosis or necroptosis pathways as well as their regulation. The possibility of their pharmacological targeting leading to the development of new strategies of interference with cell death programs via control of the high molecular weight platforms will be discussed.

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Acknowledgments

The work in the authors group was supported by grants from the Russian Science Foundation (14-25-00056), Russian Foundation for Basic Research, Russian President Fund, Dynasty Foundation, as well as the Stockholm Cancer Societies, the Swedish Childhood Cancer Foundation, the Swedish Research Council.

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Authors and Affiliations

  1. Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991, Moscow, Russia

    Alexey V. Zamaraev, Gelina S. Kopeina, Boris Zhivotovsky & Inna N. Lavrik

  2. Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden

    Boris Zhivotovsky

  3. Department of Translational Inflammation, Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany

    Inna N. Lavrik

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  1. Alexey V. Zamaraev
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  2. Gelina S. Kopeina
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Correspondence to Boris Zhivotovsky.

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Zamaraev, A.V., Kopeina, G.S., Zhivotovsky, B. et al. Cell death controlling complexes and their potential therapeutic role. Cell. Mol. Life Sci. 72, 505–517 (2015). https://doi.org/10.1007/s00018-014-1757-2

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  • DOI: https://doi.org/10.1007/s00018-014-1757-2

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