Figure 5.

p53‐Dependent cell‐cycle control is not required for TP53‐induced glycolysis regulator (TIGAR)‐mediated metabolic reprograming. (A): Overexpression of TIGAR reduces glucose consumption in p53 ^R172P hematopoietic stem cells (HSCs). Bone marrow Lineage⁻Sca‐1⁺c‐kit⁺ cells from wild‐type, Fanca ^−/−, p53 ^R172P, and Fanca ^−/− p53 ^R172P mice were transduced with lentivirus expressing mCherry‐TIGAR or mCherry alone. The sorted mCherry⁺ cells were expanded for 72 hours. The transduced cells were gated for mCherry⁺ SLAM population and assayed for glucose consumption. (B): Overexpression of TIGAR reduces PFK1 activity in p53 ^R172P HSPCs. Cells described in (A) were gated for mCherry⁺ population and assayed for PFK1 activity. (C): Overexpression of TIGAR reduces ROS production in p53 ^R172P HSPCs. Cells described in (A) were gated for mCherry⁺ SLAM population and analyzed for intracellular ROS by flow cytometry (n = 6 per group). (D): Overexpression of TIGAR reduces DNA damage in p53 ^R172P HSPCs. WCLs were extracted from mCherry⁺ cells described in (A) followed by Western blotting using antibodies against γ‐H2AX and β‐actin. Results depicted in (A) and (B) are means ± SD of three independent experiments; *, p < .05; **, p < .01.