Reprogramming of amino acid metabolism in cholangiocarcinoma: A potential target for metabolic-targeted therapy

Figure 5 Branch chain amino acid metabolism and its alteration in cholangiocarcinoma cells. The level of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) protein is stabilized by OTU deubiquitinase 4, and leucine catabolism is inhibited, leading to its accumulation in the cytosol. Upon amino acid starvation, the PPDPF protein is ubiquitously degraded upon binding to ariadne homolog 2. The up or down direction of the arrows indicates increased or decreased levels in cholangiocarcinoma cells. The dashed arrow refers to unclarified mechanisms. IL-10: Interleukin-10; IL-10R: Interleukin-10 receptor; ARIH2: Ariadne homolog 2; OTUD4: OTU deubiquitinase 4; PPDPF: Pancreatic progenitor cell differentiation and proliferation factor; BCAT2: Branched chain amino acid transaminase 2; BCKD: Branched chain ketoacid dehydrogenase kinase; MCC: Methylcrotonyl-CoA carboxylase; mTOR: Mammalian target of rapamycin; GLS1: Glutaminase 1; GDH: Glutamate dehydrogenase.