Figure 5. Regulation of one-carbon metabolism and nucleotide biosynthesis by p53 and c-Myc.

c-Myc and p53 (as well as its homologue p73) are the main trascription factors, which regulate glycolysis, one-carbon metabolism, and the nucleotide biosynthesis (shown as dark-blue ovals). c-Myc (denoted as a yellow star) is a master regulator of the key enzymes for both one-carbon metabolism and the nucleotide biosynthesis as well as its feeder pathway – glycolysis. The regulated genes are shown in black frames. Both p53 and p73 tumor suppressors (depicted as a green star) increase glutaminolysis (shown as a purple oval). They do it by activating the expression of GLS and hence enhancing the serine biosynthesis upon serine starvation. Also, p73 was shown to upregulate glucose-6-phosphate dehydrogenase thereby facilitating the pentose phosphate pathway and favoring the nucleotide biosynthesis. Also, p53 affects the expression of several micro-RNAs (shown in purple square), which target genes whose products are involved in the Folate and Methionine cycles.