MMP7 cleavage of amino-terminal CD95 death receptor switches signaling toward non-apoptotic pathways

• DOI: 10.1038/s41419-022-05352-0
• Publication Date: 2022-10-23T11:03:43Z
• Authors: Shoji F. Kenji; Keerthi Kurma; Brigitte Collet; Christelle Oblet; Laure Debure; Carmelo Di Primo; Laëtitia Minder; Franck Vérité; Yannic Danger; Mickael Jean; Aubin Penna; Nicolas Levoin; Patrick Legembre
• Keywords: 0301 basic medicine; 570; QH573-671; [SDV.CAN]Life Sciences [q-bio]/Cancer; Apoptosis; Protein Sorting Signals; Arginine; Article; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Leucine; Matrix Metalloproteinase 7; fas Receptor; Cytology

Abstract CD95 is a death receptor that can promote oncogenesis through molecular mechanisms are not fully elucidated. Although the mature membrane considered to start with arginine at position 17 after elimination of signal peptide, this also be cleaved by MMP7 upstream its leucine 37. This post-translational modification occurs in cancer cells but normal such as peripheral blood leukocytes. The non-cleaved amino-terminal region consists disordered domain and silico reconstitution suggests it might contribute aggregation thereby, regulate downstream signaling pathways. In agreement modeling analysis, comparison CD95-deficient reconstituted full-length or N-terminally truncated reveals loss impairs initial steps apoptotic while favoring induction pro-survival signals, including PI3K MAPK