MYC promotes proline biosynthesis from glutamine by upregulating critical proline synthetic enzymes at both protein and mRNA levels, such as P5C synthase (P5CS) and P5C reductase (PYCR; Fig. 2).46,48 In some proline-dependent tumor cells, oncogenic MYC activated P5CS and PYCR expression to enhance glutamine-to-proline biosynthesis, thus alleviating ER stress and promoting cellular homeostasis in proline-deprived conditions.47 Meanwhile, MYC indirectly suppresses the expression of proline oxidase/proline dehydrogenase (POX/PRODH), which catalyzes the first step in proline catabolism. This evidence concerns the gene PYCR1 and neoplasm.