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The Tumor Suppressor p53 Downregulates p107 (RBL1) Through p21-RB/E2F Signaling and Tandem E2F Sites

Khaled Azzahrani1, Faleh Alqahtani2

  • 1Central Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

International Journal of Molecular Sciences
|October 29, 2025
PubMed

Insights

The tumor suppressor p53 indirectly regulates RBL1 (p107) expression via the p21-RB-E2F pathway. This regulation relies on two specific E2F binding sites within the RBL1 promoter, impacting cell cycle control.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Transcriptional Regulation

Background:

  • RBL1 (p107), an RB-family protein, is crucial for cell cycle control and E2F repression.
  • The precise upstream regulation of RBL1, particularly by tumor suppressor pathways, is not fully understood.
  • The RBL1 promoter contains conserved E2F motifs, suggesting a role for E2F transcription factors.

Purpose of the Study:

  • To investigate the p53-dependent transcriptional regulation of the RBL1 gene.
  • To determine the contribution of the RBL1 promoter's E2F binding sites to this regulation.
  • To elucidate the role of p21 and RB/E2F complexes in mediating p53's effect on RBL1.

Main Methods:

  • Luciferase reporter assays to assess RBL1 promoter activity in synchronized cells.
  • Overexpression studies of p53 and p21.
  • Chromatin immunoprecipitation (ChIP) and DNA pull-down assays to analyze protein-DNA interactions.
  • Experiments using knockout cell lines (HCT116 p21-/-, RB-/-, LIN37-/-).

Main Results:

  • Two conserved E2F sites in the RBL1 promoter are essential for its cell cycle-dependent activation.
  • p53 represses RBL1 promoter activity in an E2F site-dependent manner, mediated by p21.
  • RB/E2F complexes are the primary repressors of the RBL1 promoter, with contributions from E2F4, p107, and p130.

Conclusions:

  • p53 indirectly controls RBL1 expression through the p21-RB-E2F pathway.
  • The two E2F binding sites within the RBL1 promoter are critical for this p53-mediated repression.
  • This mechanism highlights a novel layer of regulation for RBL1 impacting cell cycle control.
Keywords:
E2F transcription factorsRBL1cell cycle regulationp107p53

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