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. 2021 Mar 16;10(3):347. doi: 10.3390/pathogens10030347

Figure 1.

Figure 1

The degradation of p53 induced by E6 variants of human papillomavirus (HPV) 16 favors metabolic reprogramming. Variants of the European (E), African 2a (Afr2a), and Asian American (AA) sublineages decrease p53 levels through interaction with E6AP, increasing p53 degradation (red arrows), and avoiding transcriptional repression. p53 inhibits glycolysis by repressing transcription of the monocarboxylate transporter 1 (MCT1), the glucose transporters GLUT1 and GLUT4, the enzymes hexokinase 2 (HK2), phosphoglycerate mutase (PGM), pyruvate kinase 2 (PKM2), and TP53 induced glycolysis regulatory phosphatase (TIGAR). TIGAR decreases the activity of the enzyme phosphofructokinase 1 (PFK1) to target fructose-6-phosphate to the pentose phosphate (PPP) pathway. Insulin receptor (INSR) favors the translocation of GLUT4 to the membrane. Therefore, the absence of p53 due to its degradation by the effect of the variants of the E, Afr2a, and AA sublineages promotes glycolysis by activating the expression of the transporters GLUT1, GLUT4, MCT1, and the enzymes of the glycolytic pathway HK2, PGM, PKM2. Additionally, it targets fructose-6-phosphate to the PPP pathway via TIGAR for nucleotide synthesis.