Abstract
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 language | English (US) |
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Pages (from-to) | 950-966 |
Number of pages | 17 |
Journal | Trends in Cell Biology |
Volume | 33 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2023 |
Funding
We apologize to our colleagues whose work we were not able to cover in this review due to space constraints. We thank Hina Anjum for contributing to figure preparation. This work was supported by grants from the National Institutes of Health [ R01GM135587 and R01GM143334 (I.B-S.)], and by a LAM Foundation Established Investigator Award ( LAM0151E01-22 ; I.B-S.). We apologize to our colleagues whose work we were not able to cover in this review due to space constraints. We thank Hina Anjum for contributing to figure preparation. This work was supported by grants from the National Institutes of Health [R01GM135587 and R01GM143334 (I.B-S.)], and by a LAM Foundation Established Investigator Award (LAM0151E01-22; I.B-S.). The authors declare no competing interests.
Keywords
- cancer metabolism
- de novo purine and pyrimidine synthesis
- immune disorders
- metabolic vulnerability
- nucleotide signaling
- signaling pathways
ASJC Scopus subject areas
- Cell Biology