Figures & data
Figure 1. p73 isoforms and the pentose phosphate pathway. (A) Schematic representation of p73 isoforms and p53. Each p73 isoform class comprises various splicing variants (α, β, γ, etc.) that differ in their C-terminal regions. TA, transactivation domain; DBD, DNA-binding domain; OD, oligomerization domain; SAM, sterile α motif. (B) The pentose phosphate pathway and glycolysis. FBP, fructose 1,6-biphosphate; PEP, phosphoenolpyruvate; ROS, reactive oxygen species. Glycolytic pathway is indicated in blue, and oxidative pentose phosphate pathway is indicated in green.
Figure 2. Regulation of G6PD expression, NADPH levels, and DNA synthesis by p73 in H1299 cells (A and B) H1299 cells were transfected with control (−), p73, and G6PD siRNA as indicated. Protein expression was analyzed (A) and cell proliferation is shown (B). (C) NADPH levels in H1299 cells treated with control, p73, and G6PD siRNA as indicated. (D and E) H1299 cells were transfected with control, p73, and G6PD siRNA as indicated. Cells were assayed for BrdU incorporation (D). Representative images of cells stained with BrdU (E).
Figure 3. Overexpression of G6PD rescues growth defects of p73-depleted cells. (A and B) Protein expression (A) and G6PD activity (B) in H1299 cells stably overexpressing G6PD or vector control in the presence or absence of p73 siRNA are shown. (C and D) H1299 cells stably overexpressing G6PD or vector control were treated with p73 or control siRNA as indicated. Cell proliferation (C) and representative images of cells stained with crystal violet at day 6 (D) are shown
Figure 4. p73 depletion fails to affect ROS in H1299 cells (A) ROS levels in H1299 cells transfected with indicated siRNA. (B) H1299 stably overexpressing G6PD or vector control were transfected with p73 siRNA or control siRNA as indicated. ROS levels were analyzed. (C) H1299 stably overexpressing G6PD or vector control were transfected with p73 siRNA or control siRNA as indicated. Cells were treated with or without 100 µM or 250 µM H2O2 for 24 h, and cell viability was analyzed by trypan blue staining.
Figure 5. G6PD and p73 are frequently overexpressed in many human cancers (A and B) Box plot comparing TP73 and G6PD transcript levels in diffuse large B-cell lymphoma,Citation36,Citation37 uterine corpus leiomyosarcoma,Citation38 lung adenocarcinoma,Citation39,Citation40 and their counterparts. The graphs were derived from published data available through the ONCOMINE database. The differential gene expression data are centered on the median of expression levels and plotted on a log2 scale. The P value was calculated using a 2-sample t test. Whiskers indicate minimum and maximum data values that are not outliers. The number of samples (n) in each class is indicated.
