Related Experiment Video

Updated: Jun 6, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

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

Published on: March 27, 2020

Dual association by TFAP2A during activation of the p21cip/CDKN1A promoter

Angelo G Scibetta1, Ping-Pui Wong, KaYi V Chan

  • 1Centre for Tumour iology, Institute of Cancer, London, UK.

Cell Cycle (Georgetown, Tex.)
|November 19, 2010
PubMed

Insights

The transcription factor TFAP2A regulates CDKN1A gene expression independently of p53. This TFAP2A binding site is crucial for optimal p21cip/CDKN1A expression, impacting tumor suppression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The cyclin-dependent kinase inhibitor p21cip/CDKN1A is vital for cellular growth arrest and tumor suppression.
  • Dysregulation of CDKN1A is common in cancer, with p53-mediated upregulation being a key tumor-suppressive mechanism.
  • Other transcription factors, like TFAP2A, also influence CDKN1A expression.

Purpose of the Study:

  • To identify and characterize a novel AP-2 binding site in the CDKN1A promoter.
  • To investigate the role of TFAP2A in p53-independent CDKN1A expression.
  • To elucidate the temporal dynamics of TFAP2A binding to the CDKN1A promoter in response to drug induction.

Main Methods:

  • Identification of a novel AP-2 binding site within the proximal promoter of the CDKN1A gene.
  • Utilized a non-tumorigenic breast epithelial cell line model.
  • Employed Chromatin Immunoprecipitation (ChIP) to study endogenous TFAP2A and p53 binding patterns.

Main Results:

  • A novel AP-2 binding site in the CDKN1A promoter was identified, essential for p53-independent p21cip/CDKN1A expression.
  • TFAP2A binds to two promoter regions, including the proximal AP-2 site and an upstream region near the p53 binding site.
  • TFAP2A binding patterns change over time, with the proximal site gaining importance for p21cip induction.
  • TFAP2A's regulatory role differs from TFAP2C, which represses CDKN1A.

Conclusions:

  • TFAP2A plays a critical role in regulating CDKN1A expression, offering a p53-independent pathway for tumor suppression.
  • The temporal dynamics of TFAP2A binding highlight its complex role in controlling p21cip levels.
  • Understanding TFAP2A's distinct mechanism provides insights into cancer therapeutic strategies.

More Related Videos

Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells11:30

Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells

Published on: January 26, 2017

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.