ArticleMolecular and cellular biology1999
Thymidylate synthase protein and p53 mRNA form an in vivo ribonucleoprotein complex.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 94 citations in OpenAlex.
- Clinical application of biological markers for treatments of resectable non-small-cell lung cancers.British journal of cancer · 2005Trial
- Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Effects of In Utero EtOH Exposure on 18S Ribosomal RNA Processing: Contribution to Fetal Alcohol Spectrum Disorder.International journal of molecular sciences · 2023Article
- Detection of a G-Quadruplex as a Regulatory Element inInternational journal of molecular sciences · 2020Article
- A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells.International journal of molecular sciences · 2020Article
- The p53 mRNA: an integral part of the cellular stress response.Nucleic acids research · 2019Review
- MicroRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Topoisomerase I expression is associated with prognosis in postoperative non-small cell lung cancer patients.Thoracic cancer · 2016Article
- MiR-20a-5p represses multi-drug resistance in osteosarcoma by targeting the KIF26B gene.Cancer cell international · 2016Article
- Structural Analysis of Thymidylate Synthase from Kaposi's Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed.PloS one · 2016Article
- The expanding regulatory universe of p53 in gastrointestinal cancer.F1000Research · 2016Review
- Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues.Experimental and therapeutic medicine · 2015Article
- On the Contribution of Protein Spatial Organization to the Physicochemical Interconnection between Proteins and Their Cognate mRNAs.Life (Basel, Switzerland) · 2014Article
- Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients.OncoTargets and therapy · 2014Article
- Evidence of direct complementary interactions between messenger RNAs and their cognate proteins.Nucleic acids research · 2013Article
- Proteome-wide analysis reveals clues of complementary interactions between mRNAs and their cognate proteins as the physicochemical foundation of the genetic code.RNA biology · 2013Article
- Prognostic significance of miR-215 in colon cancer.Clinical colorectal cancer · 2011Article
- Translational control analysis by translationally active RNA capture/microarray analysis (TrIP-Chip).Nucleic acids research · 2010Article
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
A thymidylate synthase (TS)-ribonucleoprotein (RNP) complex composed of TS protein and the mRNA of the tumor suppressor gene p53 was isolated from cultured human colon cancer cells. RNA gel shift assays confirmed a specific interaction between TS protein and the protein-coding region of p53 mRNA, and in vitro translation studies demonstrated that this interaction resulted in the specific repression of p53 mRNA translation. To demonstrate the potential biological role of the TS protein-p53 mRNA interaction, Western immunoblot analysis revealed nearly undetectable levels of p53 protein in TS-overexpressing human colon cancer H630-R10 and rat hepatoma H35(F/F) cell lines compared to the levels in their respective parent H630 and H35 cell lines. Polysome analysis revealed that the p53 mRNA was associated with higher-molecular-weight polysomes in H35 cells compared to H35(F/F) cells. While the level of p53 mRNA expression was identical in parent and TS-overexpressing cell lines, the level of p53 RNA bound to TS in the form of RNP complexes was significantly higher in TS-overexpressing cells. The effect of TS on p53 expression was also investigated with human colon cancer RKO cells by use of a tetracycline-inducible system. Treatment of RKO cells with a tetracycline derivative, doxycycline, resulted in 15-fold-induced expression of TS protein and nearly complete suppression of p53 protein expression. However, p53 mRNA levels were identical in transfected RKO cells in the absence and presence of doxycycline. Taken together, these findings suggest that TS regulates the expression of p53 at the translational level. This study identifies a novel pathway for regulating p53 gene expression and expands current understanding of the potential role of TS as a regulator of cellular gene expression.
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