Molecular crosstalk between apoptosis, necroptosis, and survival signaling.

• Type of Material: Article
• Authors: Tom Vanden Berghe, Ghent University; William Kaiser, Emory University; Mathieu J. M. Bertrand, Ghent University; Peter Vandenabeele, Ghent University
• Language: English
• Date: 2015-10
• Publisher: Taylor & Francis Group LLC.
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC© Tom Vanden Berghe, William J Kaiser, Mathieu JM Bertrand, and Peter Vandenabeele.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.4161/23723556.2014.975093
• Title of Journal or Parent Work: Molecular & Cellular Biology
• Volume: 2
• Issue: 4
• Start Page: e975093
• End Page: e975093
• Grant/Funding Information: MB has a tenure track position within the Multidisciplinary Research Program of Ghent University (MRP, GROUP-ID consortium).; Research in the Vandenabeele group is further supported by European grants (FP6 ApopTrain, MRTNCT-035624; FP7 EC RTD Integrated Project, Apo-Sys, FP7-200767; Euregional PACT II), Belgian grants (Interuniversity Attraction Poles, IAP 6/18, IAP 7/32), Flemish grants (Research Foundation Flanders, FWO G.0875.11, FWO G.0973.11 N, FWO G.0A45.12 N, FWO G.0172.12, FWO G.0787.13N, G0C3114N and FWO KAN 31528711), Ghent University grants (MRP, GROUP-ID consortium), and grants from Flanders Institute for Biotechnology (VIB).; PV holds a Methusalem grant (BOF09/01M00709) from the Flemish Government.; TV is supported by a research grant from the Foundation against Cancer (2012-188).
• Keywords: apoptosis; Fas; tumor necrosis factor; crosstalk; RIPK1; necroptosis; FLIP; RIPK3
• Research Categories: Biology, Cell; Biology, Molecular; Health Sciences, Oncology

Abstract

Our current knowledge of the molecular mechanisms regulating the signaling pathways leading to cell survival, cell death, and inflammation has shed light on the tight mutual interplays between these processes. Moreover, the fact that both apoptosis and necrosis can be molecularly controlled has greatly increased our interest in the roles that these types of cell death play in the control of general processes such as development, homeostasis, and inflammation. In this review, we provide a brief update on the different cell death modalities and describe in more detail the intracellular crosstalk between survival, apoptotic, necroptotic, and inflammatory pathways that are activated downstream of death receptors. An important concept is that the different cell death processes modulate each other by mutual inhibitory mechanisms, serve as alternative back-up death routes in the case of a defect in the first-line cell death response, and are controlled by multiple feedback loops. We conclude by discussing future perspectives and challenges in the field of cell death and inflammation research.