Metalloprotease-mediated cleavage of CD95 Ligand.

Fiche publication

Date publication

janvier 2023

Journal

The FEBS journal

Auteurs

Membres identifiés du Cancéropôle Est :
Dr NEGRONI Luc

Tous les auteurs :
Risso V, Thomas M, Guével B, Lavigne R, Com E, Martin S, Nivet M, Pineau C, Negroni L, Lafont É, Chevet É, Eriksson LA, Le Gallo M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36694998

Résumé

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.