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HIF2 KO NSCLC cells showed high synthesis of -KG that fuels the TCA cycle, and downstream glutamate and proline

Loss G, Depner M, Ulfman LH, Joost van Neerven RJ, Hose AJ, Genuneit J, Karvonen M, Hyvrinen A, Kaulek V, Roduit C, Weber J, Lauener R, Pfefferle PI, Pekkanen J, Vaarala O, Dalphin JC, Riedler J, Braun-Fahrlnder C, von Mutius E, Ege MJ

Gastroenterol Clin Biol

Later, another study showed that a Parthenolide (PTL)-derived drug DMOCPTL directly bound to the GPX4 active site (selenocysteine 46), and led to GPX4 ubiquitination in triple-negative breast cancer cells ( Discovering the E3 ligase is also very important for understanding the regulatory mechanisms of protein ubiquitination