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Updated: Jan 15, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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Ubiquitination of Oncogenic Mutant p53 via Attenuation of Ribosome Biogenesis Machinery Effectively Inhibits

Mudassier Ahmad1,2, Sahir Sultan Alvi1,2, Haider Ahsan1

  • 1Department of Medicine and Oncology, School of Medicine, UTRGV, McAllen, Texas.

Molecular Cancer Therapeutics
|October 7, 2025
PubMed

Insights

BMH-21, an RNA polymerase I inhibitor, shows therapeutic potential against pancreatic cancer (PanCa) by selectively degrading RPA194 and targeting mutant p53. This novel approach inhibits tumor growth with minimal toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Dysregulated ribosome biogenesis and p53 mutations are key drivers in pancreatic cancer (PanCa) development.
  • Targeting these pathways offers potential therapeutic strategies for PanCa.

Purpose of the Study:

  • To investigate the therapeutic potential of BMH-21, an RNA polymerase I (Pol I) inhibitor, against pancreatic cancer.
  • To elucidate the novel molecular mechanism of BMH-21 involving RPA194 and p53 ubiquitination in PanCa.

Main Methods:

  • Utilized BMH-21, a pharmacological inhibitor of RNA polymerase I (Pol I).
  • Assessed apoptosis, cell growth inhibition, and RPA194 degradation in PanCa cells.
  • Investigated RPA194 and RPA135 recruitment to rDNA and pre-rRNA synthesis.
  • Examined p53 ubiquitination in response to BMH-21 treatment.
  • Evaluated tumor growth inhibition in orthotopic xenograft models in vivo.

Main Results:

  • BMH-21 selectively induced apoptosis and inhibited growth in PanCa cells, sparing normal cells.
  • BMH-21 treatment led to RPA194 degradation and suppressed pre-rRNA synthesis by inhibiting RPA194/RPA135 recruitment to rDNA.
  • RPA194 degradation selectively exposed mutant p53 for ubiquitination, without affecting wild-type p53.
  • BMH-21 significantly reduced pancreatic tumor growth in vivo with no observed toxicity.

Conclusions:

  • BMH-21 demonstrates significant therapeutic potential as a non-toxic agent for pancreatic cancer.
  • The drug's mechanism involves RPA194-mediated ubiquitination of mutant p53, offering a targeted treatment strategy.
  • BMH-21 represents a promising new therapeutic avenue for PanCa patients with aberrant ribosome biogenesis and mutant p53.

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