Figure 3.

Model shows the regulatory mechanism of TRIM21 in cancer metabolism. Multiple metabolic enzymes have been identified as ubiquitination substrates of TRIM21. The glycolysis is attenuated by the ubiquitination degradation of GLUT1, PFKP, G6PD and HIF1-α. De novo fatty acid synthesis and FA oxidation are also reduced by the ubiquitination degradation of FASN, GNPAT and HIF1-α. TRIM21 targets BCAT2, SHMT2 and GAC for degradation to weaken mitochondrial respiration and catalyze glutaminolysis. TRIM21 acts at multiple steps to control cancer metabolic reprogramming and reduce the increased metabolic demands in malignancies.