Related Experiment Video

Updated: Jul 13, 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

Oncogenic pathways impinging on the G2-restriction point

F Foijer1, M Simonis, M van Vliet

  • 1Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Oncogene
|August 19, 2007
PubMed

Insights

Cell cycle G2 arrest, induced by serum starvation, can be reversed by reactivating the rat sarcoma viral oncogene (RAS) and phosphatidylinositol-3 kinase pathways. These findings offer insights into cell cycle regulation and multistep carcinogenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Cells typically arrest in G1 (G1/0) without mitogenic stimuli due to the G1-restriction point.
  • Loss of the retinoblastoma gene family abrogates the G1-restriction point, revealing a second G2-restriction point.
  • Serum starvation induces G2 arrest via p27(KIP1) and p21(CIP1) inhibition of cyclins A/B1, reversible by mitogen re-addition.

Purpose of the Study:

  • To investigate the molecular pathways enabling cell cycle re-entry from G2 arrest.
  • To elucidate the role of specific signaling pathways in overcoming G2-mediated cell cycle arrest.

Main Methods:

  • Investigated cell cycle re-entry mechanisms from serum-starvation-induced G2 arrest.
  • Examined the involvement of the rat sarcoma viral oncogene (RAS) and phosphatidylinositol-3 kinase (PI3K) pathways.
  • Assessed the impact of oncogenic factors like c-MYC overexpression and activated RAS on G2-restriction point integrity.

Main Results:

  • Recovery from G2 arrest is dependent on functional RAS and PI3K signaling pathways.
  • Overexpression of c-MYC or mutational activation of RAS can overcome the G2-restriction point, leading to cell cycle abrogation.
  • Identified key molecular players and pathways that regulate exit from G2 arrest.

Conclusions:

  • The RAS and PI3K pathways are crucial for reversing G2 cell cycle arrest.
  • Oncogenic alterations can bypass the G2-restriction point, contributing to uncontrolled cell proliferation.
  • These findings provide mechanistic insights into multistep carcinogenesis and potential therapeutic targets.

More Related Videos

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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...
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.
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...