TY - JOUR
T1 - Adam10 site-dependent biology: Keeping control of a pervasive protease
AU - Tosetti, Francesca
AU - Alessio, Massimo
AU - Poggi, Alessandro
AU - Zocchi, Maria Raffaella
N1 - Funding Information:
Funding: This research was funded by the 5×1000 2015 and 5×1000 2016 from the Italian Ministry of Health to AP and the AIRC (Associazione Italiana per la Ricerca sul Cancro) IG-21648 28/11/2018.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Enzymes, once considered static molecular machines acting in defined spatial patterns and sites of action, move to different intra-and extracellular locations, changing their function. This topological regulation revealed a close cross-talk between proteases and signaling events involving post-translational modifications, membrane tyrosine kinase receptors and G-protein coupled receptors, motor proteins shuttling cargos in intracellular vesicles, and small-molecule messengers. Here, we highlight recent advances in our knowledge of regulation and function of A Disintegrin And Metalloproteinase (ADAM) endopeptidases at specific subcellular sites, or in multimolecular complexes, with a special focus on ADAM10, and tumor necrosis factor-α convertase (TACE/ADAM17), since these two enzymes belong to the same family, share selected substrates and bioactivity. We will discuss some examples of ADAM10 activity modulated by changing partners and subcellular compartmentalization, with the underlying hypothesis that restraining protease activity by spatial segregation is a complex and powerful regulatory tool.
AB - Enzymes, once considered static molecular machines acting in defined spatial patterns and sites of action, move to different intra-and extracellular locations, changing their function. This topological regulation revealed a close cross-talk between proteases and signaling events involving post-translational modifications, membrane tyrosine kinase receptors and G-protein coupled receptors, motor proteins shuttling cargos in intracellular vesicles, and small-molecule messengers. Here, we highlight recent advances in our knowledge of regulation and function of A Disintegrin And Metalloproteinase (ADAM) endopeptidases at specific subcellular sites, or in multimolecular complexes, with a special focus on ADAM10, and tumor necrosis factor-α convertase (TACE/ADAM17), since these two enzymes belong to the same family, share selected substrates and bioactivity. We will discuss some examples of ADAM10 activity modulated by changing partners and subcellular compartmentalization, with the underlying hypothesis that restraining protease activity by spatial segregation is a complex and powerful regulatory tool.
KW - ADAM
KW - ADC
KW - Cancer
KW - Exosomes
KW - Immunomodulation
KW - Metalloproteinases
KW - Signaling
KW - Subcellular trafficking
KW - Vesicles
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U2 - 10.3390/ijms22094969
DO - 10.3390/ijms22094969
M3 - Review article
AN - SCOPUS:85105408951
VL - 22
SP - 4969
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 9
ER -