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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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/3100 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:36:06Z |
| format | Article |
| id | doaj.art-2cc8bd0542a9418ea1186cc177177a4a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:36:06Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2cc8bd0542a9418ea1186cc177177a4a2023-11-22T22:51:18ZengMDPI AGCells2073-44092021-11-011011310010.3390/cells10113100Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat CellsJürgen Fritsch0Julia Frankenheim1Lothar Marischen2Timea Vadasz3Anja Troeger4Stefan Rose-John5Dirk Schmidt-Arras6Wulf Schneider-Brachert7Department of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, 93053 Regensburg, GermanyDepartment of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, 93053 Regensburg, GermanyDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Regensburg, 93053 Regensburg, GermanyDepartment of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, 93053 Regensburg, GermanyDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Regensburg, 93053 Regensburg, GermanyInstitute of Biochemistry, Christian-Albrechts-Universität zu Kiel, 24105 Kiel, GermanyDepartment of Biosciences, Paris-Lodron-University Salzburg, 5020 Salzburg, AustriaDepartment of Infection Prevention and Infectious Diseases, University Hospital of Regensburg, 93053 Regensburg, GermanySignaling 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.https://www.mdpi.com/2073-4409/10/11/3100TNF-R1ADAM17cell death |
| spellingShingle | 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 Cells TNF-R1 ADAM17 cell death |
| title | 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_short | 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 |
| topic | TNF-R1 ADAM17 cell death |
| url | https://www.mdpi.com/2073-4409/10/11/3100 |
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