PRPS activity tunes redox homeostasis in Myc-driven lymphoma.

ABSTRACT: Myc hyperactivation coordinately regulates numerous metabolic processes to drive lymphomagenesis. Here, we elucidate the temporal and functional relationships between the medley of pathways, factors, and mechanisms that cooperate to control redox homeostasis in Myc-overexpressing B cell lymphomas. We find that Myc overexpression rapidly stimulates the oxidative pentose phosphate pathway (oxPPP), nucleotide synthesis, and mitochondrial respiration, which collectively steers cellular equilibrium to a more oxidative state. We identify Myc-dependent hyperactivation of the phosphoribosyl pyrophosphate synthetase (PRPS) enzyme as a primary regulator of redox status in lymphoma cells. Mechanistically, we show that genetic inactivation of the PRPS2 isozyme, but not PRPS1, in Myc-driven lymphoma ce

SUBMITTER: MacMillan AC 

PROVIDER: S-EPMC12166406 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature