ATF4 coordinates amino acid and nucleotide synthesis with selective protein translation to ensure proper DNA replication timing in leukemia cells - PubMed
4 hours ago
- #DNA replication
- #ATF4
- #leukemia metabolism
- The transcription factor ATF4 coordinates amino acid and nucleotide metabolism with selective protein synthesis in acute leukemia cells.
- ATF4 promotes expression of enzymes for amino acid biosynthesis needed for nucleotide production and transcription of tRNA charging enzymes to support translation of replication-related proteins.
- Inhibition of ATF4 disrupts nucleotide biosynthesis and replication machinery, leading to impaired DNA replication timing, leukemia cell differentiation, and cell death.
- ATF4 plays a role in maintaining DNA replication fidelity and the differentiation blockade in leukemia cells through metabolic and translational coordination.