ArticleThe Journal of cell biology2024
Periodic changes of cyclin D1 mRNA stability are regulated by PC4 modifications in the cell cycle.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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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.
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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.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Endogenous phosphatidylcholine 16:0/20:4 increases to promote liver regeneration in hepatectomy.iScience · 2026Article
- A novel synthetic melanin as a potential anticancer agent that induces apoptosis and cyclin D downregulation through distinct pathways.The Journal of biological chemistry · 2026Article
- Regulation of mRNA decay and translation during the mammalian cell cycle.RNA (New York, N.Y.) · 2026Review
- KAT5-mediated acetylation of PC4 facilitates DNA repair by promoting chromatin reorganization.Nucleic acids research · 2025Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- The SETDB1-PC4-UPF1 post-transcriptional machinery controls periodic degradation of CENPF mRNA and maintains mitotic progression.Cell death and differentiation · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The cell cycle is a highly regulated process in which proteins involved in cell cycle progression exhibit periodic expression patterns, controlled by specific mechanisms such as transcription, translation, and degradation. However, the precise mechanisms underlying the oscillations of mRNA levels in cell cycle regulators are not fully understood. In this study, we observed that the stability of cyclin D1 (CCND1) mRNA fluctuates during the cell cycle, with increased stability during interphase and decreased stability during the M phase. Additionally, we identified a key RNA binding protein, positive coactivator 4 (PC4), which plays a crucial role in stabilizing CCND1 mRNA and regulating its periodic expression. Moreover, the binding affinity of PC4 to CCND1 mRNA is modulated by two cell cycle-specific posttranslational modifications: ubiquitination of K68 enhances binding and stabilizes the CCND1 transcript during interphase, while phosphorylation of S17 inhibits binding during the M phase, leading to degradation of CCND1 mRNA. Remarkably, PC4 promotes the transition from G1 to S phase in the cell cycle, and depletion of PC4 enhances the efficacy of CDK4/6 inhibitors in hepatocellular carcinoma, suggesting that PC4 could serve as a potential therapeutic target. These findings provide valuable insights into the intricate regulation of cell cycle dynamics.
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Registered trials
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