Related Experiment Video

Updated: Oct 4, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Dual role of p300 in the regulation of p53 stability

H Kawai1, L Nie, D Wiederschain

  • 1Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

The Journal of Biological Chemistry
|October 10, 2001
PubMed

Insights

p300 protein stabilizes p53 and its regulator MDM2. Its role in p53 stability depends on MDM2 levels, acting as a positive regulator when MDM2 is low and a negative regulator when MDM2 is high.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The role of p300 in regulating p53 stability is complex and has yielded conflicting results.
  • p300 is a known transcriptional co-activator of p53, but its influence on p53 protein levels is not fully understood.

Purpose of the Study:

  • To elucidate the dual role of p300 in regulating p53 stability.
  • To investigate how MDM2 expression influences p300's effect on p53 levels.

Main Methods:

  • Utilized a temperature-permissive p53-expressing cell line to study p53 and MDM2 dynamics.
  • Assessed p53 and MDM2 protein levels and nuclear retention under varying conditions.
  • Investigated the role of p300's acetylase activity in MDM2 stabilization.

Main Results:

  • p300 stabilizes both p53 and MDM2, enhancing the p53/MDM2 negative feedback loop.
  • p300 binding promotes p53 nuclear retention independently of its acetylase activity.
  • MDM2 stabilization by p300 requires its acetylase activity.
  • MDM2 antagonizes p300's stabilizing effect on p53.
  • p300 acts as a positive regulator of p53 stability when MDM2 levels are low, and as a negative regulator when MDM2 levels are high.

Conclusions:

  • p300 exhibits context-dependent regulation of p53 stability, influenced by MDM2 expression.
  • The findings clarify the opposing roles of p300 in p53 regulation, dependent on the MDM2 feedback loop.
  • Understanding this regulatory mechanism is crucial for cancer therapy development.

More Related Videos

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

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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.
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...