Related Experiment Video

Updated: Jul 16, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional

Reiko Hayashi1, Yuya Goto, Ryuji Ikeda

  • 1Laboratory of Molecular and Cellular Biology, Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa 214-8571, Japan.

The Journal of Biological Chemistry
|September 21, 2006
PubMed

Insights

Cell division cycle protein 4 (CDCA4) acts as a repressor in the E2F pathway, regulating cell proliferation and DNA synthesis. Its knockdown accelerates cancer cell growth, highlighting its role in cell cycle control.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The TRIP-Br family proteins regulate cell cycle progression by coactivating E2F or p53.
  • The E2F transcription factor family plays a crucial role in cell cycle control.

Purpose of the Study:

  • To identify novel E2F target genes.
  • To characterize the function of CDCA4 (SEI-3/Hepp) in the E2F pathway and cell proliferation.

Main Methods:

  • Promoter analysis of CDCA4 gene constructs.
  • Chromatin immunoprecipitation (ChIP) assays to detect E2F binding.
  • Site-directed mutagenesis to map the transactivation domain.
  • Small interfering RNA (siRNA) to knockdown CDCA4 expression.
  • Reporter gene assays to assess transcriptional activity.

Main Results:

  • CDCA4 is a novel E2F target gene, with E2F1 and E2F4 binding to its promoter.
  • CDCA4 functions as a repressor of E2F-dependent transcription, particularly through its C-terminal acidic region.
  • CDCA4 inhibits E2F-mediated transactivation and interferes with retinoblastoma protein function.
  • CDCA4 knockdown in cancer cells increases cell growth rates and DNA synthesis.
  • CDCA4 expression is induced during the G1/S phase transition.

Conclusions:

  • CDCA4 is a crucial suppressor in the E2F/retinoblastoma protein pathway, regulating cell proliferation.
  • CDCA4 plays a significant role in controlling cell cycle progression and DNA synthesis.

More Related Videos

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

Related Concept Videos

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.
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...
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.
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...