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Updated: Jul 6, 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 clathrin-mediated endocytosis by p53

Yoshie Endo1, Atsumi Sugiyama, Shun-Ai Li

  • 1Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|March 28, 2008
PubMed

Insights

The tumor-suppressing protein p53 has a newly discovered role in the cytoplasm, regulating cell surface receptor signaling. This protein binds to clathrin heavy chain (CHC) to control epidermal growth factor receptor (EGFR) endocytosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The p53 protein is a critical tumor suppressor, primarily studied for its nuclear functions.
  • The role of p53 in the cytoplasm and its involvement in cellular processes beyond DNA damage response remain largely unexplored.
  • Clathrin heavy chain (CHC) is essential for receptor-mediated endocytosis, a key pathway for regulating cell surface proteins.

Purpose of the Study:

  • To investigate the previously unknown cytosolic functions of the p53 protein.
  • To determine if p53 interacts with clathrin heavy chain (CHC) and influences clathrin-mediated endocytosis.
  • To elucidate the role of p53 in the endocytosis and signaling of the epidermal growth factor receptor (EGFR).

Main Methods:

  • Immunofluorescence microscopy to visualize p53 and CHC localization in cells.
  • RNA interference (RNAi) to ablate p53 expression and assess its impact on EGFR internalization.
  • Analysis of EGFR internalization kinetics and downstream intracellular signaling pathways.

Main Results:

  • p53 is localized in both the nucleus and cytoplasm under normal conditions and binds to CHC.
  • p53 co-localizes with CHC at the plasma membrane upon epidermal growth factor (EGF) stimulation.
  • Ablation of p53 expression significantly delays EGFR internalization and alters EGFR-mediated intracellular signaling.

Conclusions:

  • Cytosolic p53 plays a regulatory role in clathrin-mediated endocytosis.
  • p53 influences the internalization of EGFR, thereby modulating its signaling.
  • These findings reveal a novel extranuclear function of p53 in controlling receptor trafficking and signaling.

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