Faculty of Basic Medicine, MV Lomonosov Moscow State University, 119991, Moscow, Russia.
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.
Cell Mol Life Sci. 2015 Feb;72(3):505-517. doi: 10.1007/s00018-014-1757-2. Epub 2014 Oct 17.
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.
程序性细胞死亡在多细胞生物的稳态和发育调节中起着核心作用。程序性细胞死亡的失调与许多疾病有关，包括癌症和自身免疫性疾病。细胞死亡的启动发生在多蛋白复合物或高分子量平台中。这些平台内的组成、结构和分子相互作用影响细胞向生存或死亡的决策，因此定义了特定细胞死亡程序的诱导。在这里，我们详细讨论了控制细胞凋亡或坏死通路的关键细胞死亡复合物，包括 DISC、复合物 II 和 TNFRI 复合物 I/II，以及 necrosome、RIPoptosome、apoptosome 和 PIDDosome，以及它们的调节。还将讨论通过控制高分子量平台来靶向这些复合物的可能性，这可能为开发通过控制高分子量平台干扰细胞死亡程序的新策略提供可能性。
