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Signaling for survival and apoptosis in the immune system

CHAPTER SUMMARY: Signal transduction induced by tumor necrosis factor (TNF) family members and their receptors has been an intensive area of research for several years. The major impact of these studies has been the delineation of apoptotic and cell survival signaling pathways. These discoveries, co...

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Autores principales: Mak, Tak W, Yeh, Wen-Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240145/
https://www.ncbi.nlm.nih.gov/pubmed/12110144
http://dx.doi.org/10.1186/ar569
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author Mak, Tak W
Yeh, Wen-Chen
author_facet Mak, Tak W
Yeh, Wen-Chen
author_sort Mak, Tak W
collection PubMed
description CHAPTER SUMMARY: Signal transduction induced by tumor necrosis factor (TNF) family members and their receptors has been an intensive area of research for several years. The major impact of these studies has been the delineation of apoptotic and cell survival signaling pathways. These discoveries, coupled with major advances in the study of mammalian apoptotic machinery, constitute a promising blueprint of the molecular network governing the fate of all living cells. In this review, we concentrate on the fate of cells in the immune system, where regulation of cell death and cell survival is a frequent and important exercise. A small imbalance in favor of either fate can result in disastrous pathological outcomes, such as cancer, autoimmunity or immune deficiency. It is an insurmountable task to discuss all molecules reported in the literature that are implicated in lymphocyte death or survival. We have therefore focused on discoveries made by mouse gene targeting, as these studies provide the most physiologically relevant information on each molecule. We begin with a description of signaling channels initiated by TNF receptor type 1 engagement, which can lead to either cell survival or to cell death. The point of bifurcation of this pathway and the decision-making molecules FADD, TRAF2 and RIP are discussed. We then follow apoptotic and survival pathways from upstream to downstream, describing many important players involved in signal transduction. Molecules important for NF-κB and JNK/stress-activated protein kinase activation such as IKKβ, NEMO, MAP3K and TRAF6 are discussed, as is the impact of BAFF and its receptors on B-cell survival. Mouse mutants that have helped to define the mammalian apoptosis execution machinery, including animals lacking Apaf-1, caspase-3 and caspase-9, are also described. We conclude with a brief analysis of the potential therapeutic options arising from this body of work.
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spelling pubmed-32401452011-12-16 Signaling for survival and apoptosis in the immune system Mak, Tak W Yeh, Wen-Chen Arthritis Res Review CHAPTER SUMMARY: Signal transduction induced by tumor necrosis factor (TNF) family members and their receptors has been an intensive area of research for several years. The major impact of these studies has been the delineation of apoptotic and cell survival signaling pathways. These discoveries, coupled with major advances in the study of mammalian apoptotic machinery, constitute a promising blueprint of the molecular network governing the fate of all living cells. In this review, we concentrate on the fate of cells in the immune system, where regulation of cell death and cell survival is a frequent and important exercise. A small imbalance in favor of either fate can result in disastrous pathological outcomes, such as cancer, autoimmunity or immune deficiency. It is an insurmountable task to discuss all molecules reported in the literature that are implicated in lymphocyte death or survival. We have therefore focused on discoveries made by mouse gene targeting, as these studies provide the most physiologically relevant information on each molecule. We begin with a description of signaling channels initiated by TNF receptor type 1 engagement, which can lead to either cell survival or to cell death. The point of bifurcation of this pathway and the decision-making molecules FADD, TRAF2 and RIP are discussed. We then follow apoptotic and survival pathways from upstream to downstream, describing many important players involved in signal transduction. Molecules important for NF-κB and JNK/stress-activated protein kinase activation such as IKKβ, NEMO, MAP3K and TRAF6 are discussed, as is the impact of BAFF and its receptors on B-cell survival. Mouse mutants that have helped to define the mammalian apoptosis execution machinery, including animals lacking Apaf-1, caspase-3 and caspase-9, are also described. We conclude with a brief analysis of the potential therapeutic options arising from this body of work. BioMed Central 2002 2002-05-09 /pmc/articles/PMC3240145/ /pubmed/12110144 http://dx.doi.org/10.1186/ar569 Text en Copyright ©2002 BioMed Central Ltd
spellingShingle Review
Mak, Tak W
Yeh, Wen-Chen
Signaling for survival and apoptosis in the immune system
title Signaling for survival and apoptosis in the immune system
title_full Signaling for survival and apoptosis in the immune system
title_fullStr Signaling for survival and apoptosis in the immune system
title_full_unstemmed Signaling for survival and apoptosis in the immune system
title_short Signaling for survival and apoptosis in the immune system
title_sort signaling for survival and apoptosis in the immune system
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240145/
https://www.ncbi.nlm.nih.gov/pubmed/12110144
http://dx.doi.org/10.1186/ar569
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