Related Experiment Video

Updated: Sep 30, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

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

Published on: August 4, 2019

Transcriptional regulation of the mdm2 oncogene by p53 requires TRRAP acetyltransferase complexes

Penny G Ard1, Chandrima Chatterjee, Sudeesha Kunjibettu

  • 1The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Molecular and Cellular Biology
|July 26, 2002
PubMed

Insights

The p53 tumor suppressor protein cooperates with TRRAP to activate the mdm2 oncogene. This interaction is crucial for regulating gene expression and the cellular response to DNA damage.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The p53 tumor suppressor is a transcription factor crucial for cellular response to genetic damage.
  • The mdm2 oncogene is a key transcriptional target of p53, forming a negative-feedback loop via p53 degradation.
  • TRRAP is involved in transcriptional regulation and DNA repair as part of multiprotein acetyltransferase complexes.

Purpose of the Study:

  • To investigate the functional cooperation between TRRAP and p53 in activating mdm2 transcription.
  • To elucidate the biochemical mechanism by which p53 regulates mdm2 gene expression.

Main Methods:

  • In vitro binding assays to assess p53-TRRAP interaction.
  • Antisense TRRAP transfection to block p53-dependent mdm2 transcription.
  • Chromatin immunoprecipitation (ChIP) to detect TRRAP recruitment and histone acetylation at the mdm2 promoter.
  • Pharmacological inhibition of cellular deacetylases.

Main Results:

  • TRRAP functionally cooperates with p53 to activate mdm2 transcription.
  • p53 directly binds to a specific TRRAP domain.
  • Inhibition of deacetylases augments mdm2 gene transactivation.
  • Antisense TRRAP blocks p53-dependent mdm2 transcription.
  • ChIP assays show p53-dependent TRRAP recruitment to the mdm2 promoter, leading to increased histone acetylation.

Conclusions:

  • p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene promoter to activate transcription.
  • This study defines a novel mechanism for p53-mediated gene regulation involving TRRAP and histone acetylation.
  • The findings highlight a new biochemical pathway utilized by the p53 tumor suppressor.

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

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...
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...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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.
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...