ArticleNature cell biology2023
Nucleus-exported CLOCK acetylates PRPS to promote de novo nucleotide synthesis and liver tumour growth.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact.Nature communications · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Potentially Functional Variants ofCancers · 2026Article
- Circadian gene CLOCK-mediated LLPS of NBR1 and p62/SQSTM1 inhibits proliferation and migration of nasopharyngeal carcinoma.Cell death & disease · 2026Article
- Multi-Omics Landscape of Circadian Clock Dysregulation Across the Chronic Liver Disease Spectrum.International journal of molecular sciences · 2026Review
- A prognostic model based on nucleotide metabolism genes in osteosarcoma.Discover oncology · 2026Article
- p75NTR Promotes Circadian-Driven Mineralization During Tooth Development via CK2/PER2 Pathway.Cell proliferation · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- Pathogenesis and intervention strategies for metabolic dysfunction-associated fatty liver disease from the perspective of the gut-microbiota-liver axis.Frontiers in immunology · 2026Review
- CLOCK-mediated acetylation of NF-κB p65 drives immune evasion in breast cancer.Biology direct · 2025Article
- CLOCK promotes proliferation of glioblastoma cells through acetylating PRPS1/2.Journal of neuro-oncology · 2025Article
- Circadian genesJournal of Zhejiang University. Science. B · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications.Discover oncology · 2025Review
- Circadian clock gene expression: a key player in inflammation underlying chronic lung disease?ERJ open research · 2025Article
- Circadian clock communication during homeostasis and ageing.Nature reviews. Molecular cell biology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impairment of the circadian clock is linked to cancer development. However, whether the circadian clock is modulated by oncogenic receptor tyrosine kinases remains unclear. Here we demonstrated that receptor tyrosine kinase activation promotes CK2-mediated CLOCK S106 phosphorylation and subsequent disassembly of the CLOCK-BMAL1 dimer and suppression of the downstream gene expression in hepatocellular carcinoma (HCC) cells. In addition, CLOCK S106 phosphorylation exposes its nuclear export signal to bind Exportin1 for nuclear exportation. Cytosolic CLOCK acetylates PRPS1/2 K29 and blocks HSC70-mediated and lysosome-dependent PRPS1/2 degradation. Stabilized PRPS1/2 promote de novo nucleotide synthesis and HCC cell proliferation and liver tumour growth. Furthermore, CLOCK S106 phosphorylation and PRPS1/2 K29 acetylation are positively correlated in human HCC specimens and with HCC poor prognosis. These findings delineate a critical mechanism by which oncogenic signalling inhibits canonical CLOCK transcriptional activity and simultaneously confers CLOCK with instrumental moonlighting functions to promote nucleotide synthesis and tumour growth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.