fig1

Components of the human-specific, p53-mediated “kill switch” tumor suppression mechanism are usurped by human tumors, creating the possibility of therapeutic exploitation

Figure 1. The species-specific “Kill Switch” tumor suppression mechanism of humans. A: normal cell with active TP53; B: inactivation of TP53 triggers importation of dehydroepiandrosterone sulfate (DHEAS) into the affected cell, which is de-sulfated to dehydroepiandrosterone (DHEA), an uncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD). Simultaneously, glucose-6-phosphate (G6P) accumulates in the affected cell, due to an anthropoid primate-specific sequence motif (GAAT tetrad) in the G6PC promoter and importation of uric acid antioxidant into the cell by SLC2A9 ceases. The accumulation of both DHEA and G6P in the cell drive the uncompetitive inhibition of G6PD to become irreversible, leading to reactive oxygen species (ROS)-mediated cell death, extinguishing TP53 inactive cells at the single cell stage, before they can evolve into the heterogeneous tumor cell populations that have made cancer incurable up to now

Cancer Drug Resistance
ISSN 2578-532X (Online)

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All published articles will preserved here permanently:

https://www.portico.org/publishers/oae/