Metalloprotease-mediated cleavage of CD95 Ligand

Autor: Vesna Risso, Mélissa Thomas, Blandine Guével, Regis Lavigne, Emmanuelle Com, Sophie Martin, Manon Nivet, Charles Pineau, Luc Negroni, Élodie Lafont, Éric Chevet, Leif A. Eriksson, Matthieu Le Gallo
Přispěvatelé: Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Gothenburg (GU), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Eugène Marquis (CRLCC), Infrastructures en Biologie Santé et Agronomie, PLBIO2019, Institut National Du Cancer, Région Bretagne, 2018‐05973, Vetenskapsrådet
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: FEBS Journal
FEBS Journal, 2023, ⟨10.1111/febs.16737⟩
ISSN: 1742-464X
1742-4658
DOI: 10.1111/febs.16737⟩
Popis: International audience; CD95 is a member of the TNF receptor superfamily that is ubiquitously expressed in healthy and pathological tissues. Stimulation of CD95 by its physiological ligand CD95L induces its oligomerization leading in turn to the transduction of either apoptotic or non-apoptotic signals. CD95L can exist as both membrane-anchored and soluble forms (sCD95L), the latter resulting from the proteolytic cleavage of the former. Candidate proteases able to achieve CD95L cleavage were identified as matrix metalloproteases (MMP) due to their demonstrated ability to cleave other TNF superfamily ligands. The main goal of this study was to systematically identify the MMP family members capable of cleaving CD95L and subsequently determine the corresponding cleavage sites. By using different orthogonal biochemical approaches and combining them with molecular modeling, we confirmed data from the literature regarding CD95L cleavage by MMP-3 and MMP-7. Moreover, we found that MMP-2 and MMP-12 can cleave CD95L and characterized their resulting cleavage sites. This study provides a systematic approach to analyze the cleavage of CD95L, which until now had only been poorly described.
Databáze: OpenAIRE
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