Related Experiment Video

Updated: Apr 11, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.9K

MDM2 mediates p73 ubiquitination: a new molecular mechanism for suppression of p73 function

Hong Wu1, Roger P Leng1

  • 1Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.

Oncotarget
|May 31, 2015
PubMed

Insights

The tumor suppressor protein p73

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The tumor suppressor protein p73, a p53 homolog, induces apoptosis and cell cycle arrest.
  • MDM2 is activated by p73 and represses p73 functions, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism by which MDM2 represses p73 functions.
  • To investigate the role of MDM2-mediated ubiquitination in p73 regulation.

Main Methods:

  • In vivo and in vitro ubiquitination assays.
  • Co-immunoprecipitation to study protein interactions.
  • Western blotting to assess protein degradation and activity.
  • Cellular assays for apoptosis and cell cycle arrest.

Main Results:

  • MDM2 mediates p73 ubiquitination using K11, K29, and K63-linked chains.
  • MDM2 does not typically promote p73 degradation, but Itch does in Mdm2-null cells.
  • MDM2 E3 ligase activity is essential for repressing p73-dependent apoptosis and cell cycle arrest, but not transactivation.
  • A link is established between p73 ubiquitination, MDM2 E3 ligase activity, and p73 biological functions.

Conclusions:

  • MDM2's E3 ligase activity is crucial for inhibiting p73's tumor-suppressive roles.
  • Ubiquitination by MDM2, potentially involving Itch, regulates p73 stability and function.
  • This study reveals a novel regulatory pathway for p73 involving MDM2-mediated ubiquitination.
Keywords:
oncogeneprotein degradationtumor suppressorubiquitin E3 ligaseubiquitination

More Related Videos

Detection of Protein Ubiquitination09:00

Detection of Protein Ubiquitination

Published on: August 19, 2009

43.9K
Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

3.8K

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...
5.4K
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....
9.9K
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...
9.3K
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...
3.0K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
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...
3.4K