A disintegrin and metalloprotease 17 (ADAM17), also called TACE (tumor necrosis factor-α-converting enzyme), is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases, activated by substrate presentation.

ADAM17 plays a key role in activating IL-6 trans-signaling pathway, as it sheds the ectodomain of IL-6R, both in vitro and in vivo [27,28]. Soluble IL-6R (sIL-6R) retains its ability to bind IL-6, preventing it from binding to the membrane-tethered form of the receptor.

Nov 13, 2024 · The functional ADAM17 is involved in the shedding of the ectodomain characterizing many substrates belonging to growth factors, cytokines, receptors, and adhesion molecules. The ADAM17-dependent pathways are known to be crucial in tumor development and progression and in the modulation of many pathological and physiological processes.

Oct 12, 2016 · ADAM17 is mainly endocytosed via a clathrin-dependent pathway. Which endocytic pathway is responsible for ADAM17 internalisation?

This review provides an overview of the role of ADAM17 in EMT-associated pathways, highlighting new therapeutic perspectives on fibrotic diseases and cancer. As this review underlines, several studies on ADAM17 structure and function in …

Aug 4, 2023 · ADAM17 is involved in the cleavage and shedding of at least 80 known membrane-tethered proteins, which subsequently modulate several intracellular signaling pathways, and therefore alter cell behavior.

Knowledge of the substrates of ADAM17 helped provide a pathway as to what would be the best use of an ADAM17 inhibitor in the clinic. Researchers have now developed selective inhibitors after learning early on of the failures of small molecules that also targeted the matrix metalloproteinase family [ 13 – 15 ].

Aug 1, 2011 · Activated ADAM17 is capable of controlling pathways that are biologically distinct. On one hand, cleavage of substrates, including TNFα, IL-6R and L-selectin, can be considered pro-inflammatory because they stimulate both innate and acquired immune responses ( Figure 3 ).

Feb 10, 2021 · Neuron-associated ADAM17 may have a beneficial effect by triggering the non-amyloidogenic pathway of APP processing, while microglia-associated ADAM17 can be detrimental for its ability to release TNF and sustain chronic inflammatory responses.

Dec 18, 2024 · The functional ADAM17 is involved in the shedding of the ectodomain characterizing many substrates belonging to growth factors, cytokines, receptors, and adhesion molecules. The ADAM17-dependent pathways are known to be crucial in tumor development and progression and in the modulation of many pathological and physiological processes.