ArticleCell reports2025
mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Functional characterization of the 9q34.13 locus identifies RAPGEF1 as a candidate gene modulating risk for melanoma and nevi via RAS activation.American journal of human genetics · 2026Article
- Mitochondrial metabolism determines chemotherapy sensitivity in colorectal cancer.Nature metabolism · 2026Article
- Wdr26 insufficiency causes Skraban-Deardorff syndrome-like neurodevelopmental deficits in mice.The Journal of clinical investigation · 2026Article
- Proteomic Profiling Reveals How Physiological Media Reshape Cancer Cell Proteomes and Signaling Networks.Molecular & cellular proteomics : MCP · 2026Article
- The MOGA multi-modal framework based on graph augmentation networks for drug response prediction.iScience · 2026Article
- Article
- Proteomic analysis of stone-containing and non-stone human renal papillae reveals novel insights and therapeutic targets.Urolithiasis · 2026Article
- Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis.bioRxiv : the preprint server for biology · 2026Article
- UCK2 Drives Lung Adenocarcinoma Progression and Immune Dysregulation via the RHEB/mTOR Signaling Axis.Oncology research · 2026Article
- Human clearance systems have a layered architecture across tissues and cell types that supports varied proteome compositions.Autophagy · 2026Article
- Targeting tubular NAT10 ameliorates the renal Tubulointerstitial Fibrosis in Obstructive and Folic Acid-Induced Nephropathy.International journal of biological sciences · 2026Article
- Loss of RanBP9 cooperates with p53 deficiency to promote sarcomagenesis.Frontiers in oncology · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Mapping transcriptomic signatures downstream of mitochondrial superoxide dismutase SOD2 in OVCA433 multicellular aggregates.Advances in redox research · 2025Article
- The many faces of the GID/CTLH E3 ligase complex.Biochemical Society transactions · 2025Review
- Transition From a High-Sugar and Butter to a Standard Diet Leads to Cecal Dysbiosis, Disrupts Intestinal Homeostasis, and Favors Increased Ethanol Consumption and Preference.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- WDR26-related Skraban-Deardorff syndrome: clinical, genetic and pathomechanistic insights.European journal of medical research · 2025Article
- Article
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Authors and funding
4 authors.
Funding
Abstract
One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target of rapamycin complex 1 (mTORC1) promotes pyrimidine synthesis by activating the de novo pathway for cell proliferation. However, the involvement of mTORC1 in regulating the salvage pathway remains unclear. Here, we report that mTORC1 controls the half-life of uridine cytidine kinase 2 (UCK2), the rate-limiting enzyme in the salvage pathway. Specifically, UCK2 is degraded via the CTLH-WDR26 E3 complex during mTORC1 inhibition, which is prevented when mTORC1 is active. We also find that UCK1, an isoform of UCK2, affects the turnover of UCK2 by influencing its cellular localization. Importantly, altered UCK2 levels through the mTORC1-CTLH E3 pathway affect pyrimidine salvage and the efficacy of pyrimidine analog prodrugs. Therefore, mTORC1-CTLH E3-mediated degradation of UCK2 adds another layer of complexity to mTORC1's role in regulating pyrimidine metabolism.
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