Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1

Abstract Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis....

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Autores principales:	September R. Mihaly, Yosuke Sakamachi, Jun Ninomiya-Tsuji, Sho Morioka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2056cc721a4243bf8b14c0331b0af806
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spelling	oai:doaj.org-article:2056cc721a4243bf8b14c0331b0af8062021-12-02T15:06:24ZNoncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 110.1038/s41598-017-03112-12045-2322https://doaj.org/article/2056cc721a4243bf8b14c0331b0af8062017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03112-1https://doaj.org/toc/2045-2322Abstract Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis. Indeed, necroptosis is triggered by caspase inhibition to ensure cell death. Here we identified a previously uncharacterized cell death pathway regulated by TAK1, which is unexpectedly provoked by inhibition of caspase activity and necroptosis cascades. Ablation of TAK1 triggers spontaneous death in macrophages. Simultaneous inhibition of caspases and RIPK3 did not completely restore cell viability. Previous studies demonstrated that loss of TAK1 in fibroblasts causes TNF-induced apoptosis and that additional inhibition of caspase leads to necroptotic cell death. However, we surprisingly found that caspase and RIPK3 inhibitions do not completely suppress cell death in Tak1-deficient cells. Mechanistically, the execution of the third cell death pathway in Tak1-deficient macrophages and fibroblasts were mediated by RIPK1-dependent rapid accumulation of reactive oxygen species (ROS). Conversely, activation of RIPK1 was sufficient to induce cell death. Therefore, loss of TAK1 elicits noncanonical cell death which is mediated by RIPK1-induced oxidative stress upon caspase and necroptosis inhibition to further ensure induction of cell death.September R. MihalyYosuke SakamachiJun Ninomiya-TsujiSho MoriokaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q September R. Mihaly Yosuke Sakamachi Jun Ninomiya-Tsuji Sho Morioka Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
description	Abstract Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis. Indeed, necroptosis is triggered by caspase inhibition to ensure cell death. Here we identified a previously uncharacterized cell death pathway regulated by TAK1, which is unexpectedly provoked by inhibition of caspase activity and necroptosis cascades. Ablation of TAK1 triggers spontaneous death in macrophages. Simultaneous inhibition of caspases and RIPK3 did not completely restore cell viability. Previous studies demonstrated that loss of TAK1 in fibroblasts causes TNF-induced apoptosis and that additional inhibition of caspase leads to necroptotic cell death. However, we surprisingly found that caspase and RIPK3 inhibitions do not completely suppress cell death in Tak1-deficient cells. Mechanistically, the execution of the third cell death pathway in Tak1-deficient macrophages and fibroblasts were mediated by RIPK1-dependent rapid accumulation of reactive oxygen species (ROS). Conversely, activation of RIPK1 was sufficient to induce cell death. Therefore, loss of TAK1 elicits noncanonical cell death which is mediated by RIPK1-induced oxidative stress upon caspase and necroptosis inhibition to further ensure induction of cell death.
format	article
author	September R. Mihaly Yosuke Sakamachi Jun Ninomiya-Tsuji Sho Morioka
author_facet	September R. Mihaly Yosuke Sakamachi Jun Ninomiya-Tsuji Sho Morioka
author_sort	September R. Mihaly
title	Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
title_short	Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
title_full	Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
title_fullStr	Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
title_full_unstemmed	Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1
title_sort	noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of tgfβ-activated kinase 1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2056cc721a4243bf8b14c0331b0af806
work_keys_str_mv	AT septemberrmihaly noncanonicalcelldeathprogramindependentofcaspaseactivationcascadeandnecroptoticmodulesiselicitedbylossoftgfbactivatedkinase1 AT yosukesakamachi noncanonicalcelldeathprogramindependentofcaspaseactivationcascadeandnecroptoticmodulesiselicitedbylossoftgfbactivatedkinase1 AT junninomiyatsuji noncanonicalcelldeathprogramindependentofcaspaseactivationcascadeandnecroptoticmodulesiselicitedbylossoftgfbactivatedkinase1 AT shomorioka noncanonicalcelldeathprogramindependentofcaspaseactivationcascadeandnecroptoticmodulesiselicitedbylossoftgfbactivatedkinase1
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Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1

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