University of Illinois at Chicago
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Externalized glycolytic enzymes are novel, conserved, and early biomarkers of apoptosis

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posted on 2013-11-15, 00:00 authored by David S. Ucker, Mohit Raja Jain, Goutham Pattabiraman, Karol Palasiewicz, Raymond B. Birge, Hong Li
The intriguing cell biology of apoptotic cell death results in the externalization of numerous autoantigens on the apoptotic cell surface, including protein determinants for specific recognition, linked to immune responses. Apoptotic cells are recognized by phagocytes and trigger an active immunosuppressive response (“innate apoptotic immunity” [IAI]) even in the absence of engulfment. IAI is responsible for the lack of inflammation associated normally with the clearance of apoptotic cells; its failure also has been linked to inflammatory and autoimmune pathology, including systemic lupus erythematosis (SLE) and rheumatic diseases. Apoptotic recognition determinants underlying IAI have yet to be identified definitively; we argue that these molecules are surface-exposed (during apoptotic cell death), ubiquitously-expressed, protease-sensitive, evolutionarily-conserved, and resident normally in viable cells (“SUPER”). Taking independent and unbiased quantitative proteomic approaches to characterize apoptotic cell surface proteins and identify candidate SUPER determinants, we made the surprising discovery that components of the glycolysis pathway are enriched on the apoptotic cell surface. Our data demonstrate that glycolytic enzyme externalization is a common and early aspect of cell death in different cell types triggered to die with distinct suicidal stimuli. Exposed glycolytic enzyme molecules meet the criteria for IAI-associated SUPER determinants. In addition, our characterization of the apoptosis-specific externalization of glycolytic enzyme molecules may provide insight into the significance of previously reported cases of plasminogen binding to α-enolase on mammalian cells, as well as mechanisms by which commensal bacteria and pathogens maintain immune privilege.


This research is supported in part by NIH grants AG029633 to DSU and NS046593 to HL (for the support of a UMDNJ Neuroproteomics Core Facility).


Publisher Statement

This research was originally published in Journal of Biological Chemistry. Ucker DS, Jain MR, Pattabiraman G, Palasiewicz K, Birge RB, Li H. Externalized glycolytic enzymes are novel, conserved, and early biomarkers of apoptosis. Journal of Biological Chemistry. 2012 Mar 23;287(13):10325-43. © the American Society for Biochemistry and Molecular Biology


American Society for Biochemistry and Molecular Biology


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