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...

Full description

Saved in:

Bibliographic Details
Published in:	Cells (Basel, Switzerland) Vol. 10; no. 11; p. 3100
Main Authors:	Fritsch, Jürgen, Frankenheim, Julia, Marischen, Lothar, Vadasz, Timea, Troeger, Anja, Rose-John, Stefan, Schmidt-Arras, Dirk, Schneider-Brachert, Wulf
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 10-11-2021 MDPI
Subjects:	ADAM17 ADAM17 Protein - antagonists & inhibitors ADAM17 Protein - deficiency ADAM17 Protein - metabolism Amyloid Precursor Protein Secretases - metabolism Antibodies Apoptosis Cell culture Cell Death Cell fate Cell Survival CRISPR Cytoplasm Endocytosis Flow cytometry Humans Inflammatory diseases Internalization Jurkat Cells Ligands MCF-7 Cells Metalloproteinase Models, Biological NF-kappa B - metabolism Receptors, Tumor Necrosis Factor, Member 25 - metabolism Receptors, Tumor Necrosis Factor, Type I - metabolism Signal Transduction TNF-R1 Tumor Necrosis Factor-alpha - pharmacology Tumor necrosis factor-α U937 Cells Germany cell death ADAM17 TNF-R1
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells10113100