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. Author manuscript; available in PMC: 2022 Sep 16.
Published in final edited form as: Mol Cell. 2021 Jul 20;81(18):3833–3847.e11. doi: 10.1016/j.molcel.2021.06.027

Figure 7. Working model:

Figure 7.

mitochondrial mutant IDH2 activity is commonly restricted through inhibitory K413-acetylation in human AML cells, which optimizes mutant IDH2-dependent transformation by producing sufficient 2-HG for transformation and avoiding cytotoxic accumulation of intracellular 2-HG to AML cells. FLT3 promotes mutant IDH2 lysine acetylation by phosphorylating mutant IDH2, which enhances acetyltransferase ACAT1 recruitment to mutant IDH2. In addition, FLT3 simultaneously activates ACAT1 but inhibits deacetylase SIRT3 through direct tyrosine phosphorylation, which also contributes to mutant IDH2 lysine acetylation.