Related Experiment Video

Updated: Aug 24, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Ubiquitin-dependent degradation of p73 is inhibited by PML

Francesca Bernassola1, Paolo Salomoni, Andrew Oberst

  • 1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.

The Journal of Experimental Medicine
|June 9, 2004
PubMed

Insights

The promyelocytic leukemia (PML) protein stabilizes tumor suppressor p73 by inhibiting its degradation. PML enhances p73

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • p73 is a homologue of the tumor suppressor p53.
  • The stability of tumor suppressor proteins is critical for their function.
  • The ubiquitin-proteasome pathway and post-translational modifications regulate protein stability.

Purpose of the Study:

  • To investigate the regulation of p73 stability.
  • To elucidate the role of the promyelocytic leukemia (PML) protein in p73 regulation.
  • To understand the molecular mechanisms underlying p73 stabilization by PML.

Main Methods:

  • Western blotting to assess protein levels and stability.
  • Immunoprecipitation to study protein interactions.
  • Cellular localization studies using immunofluorescence microscopy.
  • Analysis of primary cells from Pml knockout mice.

Main Results:

  • p73 stability is regulated by the ubiquitin-proteasome pathway.
  • PML protein inhibits p73 degradation in a PML-nuclear body (NB)-dependent manner.
  • p38 kinase-mediated phosphorylation is required for p73 recruitment to PML-NBs and stabilization.
  • p300-mediated acetylation protects p73 from ubiquitinylation, and PML enhances this acetylation.
  • PML potentiates p73 transcriptional and proapoptotic activities, which are impaired in Pml-/- cells.

Conclusions:

  • PML plays a crucial role in stabilizing p73 through modulating its degradation and acetylation.
  • PML-dependent stabilization of p73 enhances its tumor suppressor functions.
  • These findings provide insights into the molecular network regulating tumor suppression.

More Related Videos

Assays for the Degradation of Misfolded Proteins in Cells10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...