Negative transcriptional regulation of urea cycle enzymes

TP53 tetramer binds to sites in the promoter regions of the OTC, CPS1 and ARG1 genomic regions to repress transcription as assessed by ChIP and reporter gene assay. Through transcriptional downregulation of these urea cycle enzymes, TP53 increases cellular ammonia levels, ultimately leading to increased proliferation through elevated polyamine synthesis (Li et al, 2019; reviewed in Holbert et al, 2022). Elevated ammonia promotes increased translation of ornithine decarboxylase (ODC), the first and rate limiting enzyme in polyamine biosynthesis (Li et al, 2019; Dufe et al, 2007; Kanerva et al, 2008; reviewed in Holbert et al, 2022).

Summary from Reactome (R-HSA-9988426), read 2026-09-23.