Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells

Signaling via death receptor family members such as TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Pro-survival signaling is mediated via TNF-R1 complex I at the cellular plasma membrane. Cell death induction requires complex IIa/b or necro...

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Autores principales:	Jürgen Fritsch, Julia Frankenheim, Lothar Marischen, Timea Vadasz, Anja Troeger, Stefan Rose-John, Dirk Schmidt-Arras, Wulf Schneider-Brachert
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TNF-R1 ADAM17 cell death Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2cc8bd0542a9418ea1186cc177177a4a
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spelling	oai:doaj.org-article:2cc8bd0542a9418ea1186cc177177a4a2021-11-25T17:11:30ZRoles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells10.3390/cells101131002073-4409https://doaj.org/article/2cc8bd0542a9418ea1186cc177177a4a2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3100https://doaj.org/toc/2073-4409Signaling via death receptor family members such as TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Pro-survival signaling is mediated via TNF-R1 complex I at the cellular plasma membrane. Cell death induction requires complex IIa/b or necrosome formation, which occurs in the cytoplasm. In many cell types, full apoptotic or necroptotic cell death induction requires the internalization of TNF-R1 and receptosome formation to properly relay the signal inside the cell. We interrogated the role of the enzyme A disintegrin and metalloprotease 17 (ADAM17)/TACE (TNF-α converting enzyme) in death receptor signaling in human hematopoietic cells, using pharmacological inhibition and genetic ablation. We show that in U937 and Jurkat cells the absence of ADAM17 does not abrogate, but rather increases TNF mediated cell death. Likewise, cell death triggered via DR3 is enhanced in U937 cells lacking ADAM17. We identified ADAM17 as the key molecule that fine-tunes death receptor signaling. A better understanding of cell fate decisions made via the receptors of the TNF-R1 superfamily may enable us, in the future, to more efficiently treat infectious and inflammatory diseases or cancer.Jürgen FritschJulia FrankenheimLothar MarischenTimea VadaszAnja TroegerStefan Rose-JohnDirk Schmidt-ArrasWulf Schneider-BrachertMDPI AGarticleTNF-R1ADAM17cell deathBiology (General)QH301-705.5ENCells, Vol 10, Iss 3100, p 3100 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TNF-R1 ADAM17 cell death Biology (General) QH301-705.5
spellingShingle	TNF-R1 ADAM17 cell death Biology (General) QH301-705.5 Jürgen Fritsch Julia Frankenheim Lothar Marischen Timea Vadasz Anja Troeger Stefan Rose-John Dirk Schmidt-Arras Wulf Schneider-Brachert Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
description	Signaling via death receptor family members such as TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Pro-survival signaling is mediated via TNF-R1 complex I at the cellular plasma membrane. Cell death induction requires complex IIa/b or necrosome formation, which occurs in the cytoplasm. In many cell types, full apoptotic or necroptotic cell death induction requires the internalization of TNF-R1 and receptosome formation to properly relay the signal inside the cell. We interrogated the role of the enzyme A disintegrin and metalloprotease 17 (ADAM17)/TACE (TNF-α converting enzyme) in death receptor signaling in human hematopoietic cells, using pharmacological inhibition and genetic ablation. We show that in U937 and Jurkat cells the absence of ADAM17 does not abrogate, but rather increases TNF mediated cell death. Likewise, cell death triggered via DR3 is enhanced in U937 cells lacking ADAM17. We identified ADAM17 as the key molecule that fine-tunes death receptor signaling. A better understanding of cell fate decisions made via the receptors of the TNF-R1 superfamily may enable us, in the future, to more efficiently treat infectious and inflammatory diseases or cancer.
format	article
author	Jürgen Fritsch Julia Frankenheim Lothar Marischen Timea Vadasz Anja Troeger Stefan Rose-John Dirk Schmidt-Arras Wulf Schneider-Brachert
author_facet	Jürgen Fritsch Julia Frankenheim Lothar Marischen Timea Vadasz Anja Troeger Stefan Rose-John Dirk Schmidt-Arras Wulf Schneider-Brachert
author_sort	Jürgen Fritsch
title	Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
title_short	Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
title_full	Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
title_fullStr	Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
title_full_unstemmed	Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells
title_sort	roles for adam17 in tnf-r1 mediated cell death and survival in human u937 and jurkat cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2cc8bd0542a9418ea1186cc177177a4a
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Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells

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