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- W4313374673 abstract "Abstract Autocrine engagement of the complement receptor CD46, driven by T cell receptor (TCR) activation on human CD4 T cells, is critical for human Th1 induction: Processing of the intracellular CD46 domains by gamma-secretase and their nuclear translocation mediates the expression of nutrient transporters and enables metabolic reprogramming required for cell growth, expansion and effector function. How, at the molecular level, CYT-1 enables this fundamental cellular adaptation remains unknown. Co-immunoprecipitation experiments with antibodies against cleaved CYT-1 revealed an association of CYT-1 with the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). A strong, dose-dependent interaction was confirmed via ELISA and Microscale Thermophoresis- (MST−) based experiments in vitro and via proximity ligation assays (PLAs) in CD4 T cells ex vivo. Unexpectedly, subsequent experiments demonstrated that CYT-1 did not affect metabolic activity of GAPDH but rather fostered its des-oligomerization. CYT-1-driven des-oligomerization of GAPDH ‘unleashed’ its non-canonical ‘moonlighting’ function: CYT-1-generated GAPDH monomers displayed augmented mRNA binding abilities and stabilized metabolic mRNAs in living CD4 T cells. Importantly, this CYT-1capacity is not confined to GAPDH: CYT-1 binds and des-oligomerizes several other glycolytic enzymes. These data identify CD46 as a ‘shape-shifter’ of glycolytic enzyme activity, critically balancing the canonical (glycolysis) versus non-canonical (e.g. posttranscriptional regulation) activity – further substantiating the notion that autocrine complement is a critical regulator of normal cell physiology." @default.
- W4313374673 created "2023-01-06" @default.
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- W4313374673 date "2020-05-01" @default.
- W4313374673 modified "2023-09-27" @default.
- W4313374673 title "A ‘sweet spot’ for complement receptor CD46 activity: direct regulation of glycolytic vs. moonlighting functions of glycolytic enzymes" @default.
- W4313374673 doi "https://doi.org/10.4049/jimmunol.204.supp.78.19" @default.
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