Related Experiment Video

Updated: Jul 16, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma

M E Crosby1, J Jacobberger, D Gupta

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland, OH, USA.

Oncogene
|October 18, 2006
PubMed

Insights

The retinoblastoma (pRB) protein family member E2F4 enforces a stable G(2) cell cycle arrest following radiation. This response minimizes DNA damage propagation, enhancing cell survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Retinoblastoma (pRB) proteins and E2F transcription factors regulate cell cycle transitions.
  • The role of pRB family/E2F complexes, specifically p130/E2F4, in response to genotoxic stress is not well understood.

Purpose of the Study:

  • To investigate the function of E2F4 in the genotoxic stress response.
  • To elucidate the mechanism by which E2F4 influences cell cycle arrest and survival after DNA damage.

Main Methods:

  • Cells were treated with radiation, and E2F4 localization and cell cycle arrest were analyzed.
  • Small interference RNA (siRNA) was used to knockdown E2F4 expression.
  • Oligonucleotide microarray and chromatin immunoprecipitation were employed to identify E2F4 targets.

Main Results:

  • E2F4 colocalized with p130 in the nucleus during radiation-induced G(2) arrest.
  • Knockdown of E2F4 sensitized cells to irradiation, increasing DNA damage and cell death.
  • E2F4 was found to repress the expression of mitotic genes like Bub3 and Pttg1.

Conclusions:

  • E2F4 plays a critical role in enforcing a stable G(2) arrest in response to radiation.
  • E2F4-mediated gene repression contributes to cell survival by preventing the propagation of cells with irreparable DNA damage.

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

Proximity Ligand Assay to Localize Proteins in DNA Damage Sites09:39

Proximity Ligand Assay to Localize Proteins in DNA Damage Sites

Published on: August 2, 2024

Related Concept Videos

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.
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...