Fig. 5From: Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cellsSome metabolic and signalling circuits that intersect with glutaminase isoenzymes. This network schematic representation shows both glutaminase isoenzymes, GLS and GLS2, executing a dual function. First, glutaminase is the limiting enzyme in glutaminolysis to generate glutamate from glutamine, that can be used for GSH synthesis, the most important intracellular antioxidant. Second, both isoenzymes can interact with other proteins and signalling pathways. GLS is regulated by the oncogenic transcription factor c-Myc and activates mTORC1, which is a major positive regulator of the Warburg effect. Tumour suppressor factor p53 is hampered by GLS, but stimulates GLS2. GLS2 blocks PI3K/AKT signalling pathway while interacts and stabilizes Dicer to mature several miRNAs which repress Snail favouring Warburg effect of tumour cells, and impacting oxidative status. P53 connects GLS, GLS2, microRNAs, ROS homeostasis and cancer. GLS glutaminase isoenzyme, GLS2Â glutaminase 2Â isoenzyme, GSHÂ glutathione, LRH-1Â nuclear receptor liver receptor homolog 1, mTORC1Â mammalian target of rapamycin complex 1, PI3K/AKTÂ phosphatidylinositol-3-kinase/protein kinase B, ROS reactive oxygen specieBack to article page