Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress

Annalisa Pecoraro1, Pietro Carotenuto2, Giulia Russo3

  • 1Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Scientific Reports
|October 30, 2019
PubMed

Insights

Human ribosomal protein L3 (uL3) regulates cell cycle progression by affecting G1/S transition genes. This study reveals a new pathway involving uL3, E2F1, and Cyclin D1 in cancer treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Cycle Regulation

Background:

  • Cancer treatment strategies often target cell cycle regulation.
  • Extra-ribosomal functions of human ribosomal protein L3 (uL3) are implicated in DNA repair, cell cycle arrest, and apoptosis.

Purpose of the Study:

  • To investigate the role of uL3 in regulating cell cycle progression.
  • To identify the molecular mechanisms by which uL3 influences cell cycle genes.

Main Methods:

  • Luciferase assays to assess E2F1 promoter activity.
  • Western blotting to measure Cyclin D1 mRNA and protein levels.
  • Co-immunoprecipitation to detect protein-protein interactions between uL3 and PARP-1.

Main Results:

  • uL3 is essential for the activation of G1/S transition genes.
  • uL3 negatively regulates E2F1 promoter activity.
  • uL3 interacts with PARP-1, impacting E2F1 transcriptional activity and reducing Cyclin D1 levels.

Conclusions:

  • A novel pathway mediated by uL3, involving E2F1 and Cyclin D1, regulates cell cycle progression.
  • uL3's extra-ribosomal functions present a potential new therapeutic target in cancer treatment.

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