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Updated: Jun 21, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Regulation of p53 expression, phosphorylation and subcellular localization by a G-protein-coupled receptor

L Solyakov1, E Sayan, J Riley

  • 1Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.

Oncogene
|August 4, 2009
PubMed

Insights

G-protein-coupled receptors (GPCRs) can influence cancer drug effectiveness. This study shows M(3)-muscarinic receptor activation protects cells from chemotherapy by altering p53 protein regulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • G-protein-coupled receptors (GPCRs) are established drug targets, but their role in cancer therapy is underexplored.
  • The M(3)-muscarinic receptor, a G(q/11)-coupled GPCR, is investigated for its potential in cancer treatment.

Purpose of the Study:

  • To investigate the role of the M(3)-muscarinic receptor in regulating apoptosis induced by chemotherapeutic agents.
  • To determine how M(3)-muscarinic receptor stimulation affects the p53 pathway in cancer cells.

Main Methods:

  • Utilized human neuroblastoma (SH-SY5Y) and Chinese hamster ovary (CHO) cells.
  • Stimulated endogenous and ectopically expressed M(3)-muscarinic receptors.
  • Assessed apoptosis, p53 expression, p53 translocation, and p53 phosphorylation in response to etoposide and receptor stimulation.

Main Results:

  • M(3)-muscarinic receptor stimulation inhibited etoposide-induced apoptosis in both cell types.
  • In CHO cells, receptor activation modulated p53 expression levels.
  • In SH-SY5Y cells, receptor activation inhibited p53 mitochondrial translocation and phosphorylation at specific sites.

Conclusions:

  • GPCRs, specifically the M(3)-muscarinic receptor, can modulate cancer chemotherapeutic efficacy.
  • The mechanism involves regulating p53 expression, trafficking, and modification in a cell-type-dependent manner.
  • This suggests GPCRs as potential targets for enhancing cancer therapy.

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