Regulation of nucleotide metabolism in cancers and immune disorders

Eunus S. Ali, Issam Ben-Sahra

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


Nucleotides are the foundational elements of life. Proliferative cells acquire nutrients for energy production and the synthesis of macromolecules, including proteins, lipids, and nucleic acids. Nucleotides are continuously replenished through the activation of the nucleotide synthesis pathways. Despite the importance of nucleotides in cell physiology, there is still much to learn about how the purine and pyrimidine synthesis pathways are regulated in response to intracellular and exogenous signals. Over the past decade, evidence has emerged that several signaling pathways [Akt, mechanistic target of rapamycin complex I (mTORC1), RAS, TP53, and Hippo-Yes-associated protein (YAP) signaling] alter nucleotide synthesis activity and influence cell function. Here, we examine the mechanisms by which these signaling networks affect de novo nucleotide synthesis in mammalian cells. We also discuss how these molecular links can be targeted in diseases such as cancers and immune disorders.

Original languageEnglish
Pages (from-to)950-966
Number of pages17
JournalTrends in Cell Biology
Issue number11
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Ltd


  • cancer metabolism
  • de novo purine and pyrimidine synthesis
  • immune disorders
  • metabolic vulnerability
  • nucleotide signaling
  • signaling pathways

ASJC Scopus subject areas

  • Cell Biology


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