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Distinct Necrotic Protein Cleavages as Biomarkers for Necrosis

ABSTRACT: Apoptosis is executed by caspase-mediated proteolytically cleavage. In contrast, we know very little regarding the involvement of proteolytic cleavage in necrosis. In particular, we still lack mechanistic insights and biomarkers for necrosis caused by overwhelming stress such as ferroptosis. Here we found that necrosis, such as necroptosis and ferroptosis, led to characteristic necrotic lamin-B1 cleavage distinct from that of apoptotic lamin-B1 cleavage, while both apoptotic and necrotic cleavages of lamin-B1 were found in pyroptosis. Using neo-N-terminomic analysis, we identified a substantial set of protein substrates proteolytically cleaved after Arg/Lys residues in necrosis mediated by extracellular trypsin-like proteases. Necrotic protein cleavage is involved in mediating nuclear morphological change and loss of chromatin DNA in necrosis and the clearance of necrotic dead cells by phagocytosis. Defective necrotic protein cleavage promotes autoimmunity. Finally, we developed antibodies recognizing specific necrotic cleavage events as biomarkers for necrosis in cells and in vivo under pathological conditions.

ORGANISM(S): Homo Sapiens Mus Musculus

SUBMITTER: Yaoyang Zhang

PROVIDER: PXD069280 | iProX | Thu Oct 09 00:00:00 BST 2025

REPOSITORIES: iProX

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