Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.0K
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...
9.0K
Abnormal Proliferation02:23

Abnormal Proliferation

4.4K
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...
4.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

35.1K
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.
35.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.5K
2.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

4.6K
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...
4.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Patterns of Response to Immune Checkpoint Inhibitors in Sarcomas With High Tumor Burden and/or Mismatch Repair Deficiency.

JCO precision oncology·2026
Same author

Quantifying single-cell responses to irradiation in 3D.

Frontiers in bioengineering and biotechnology·2026
Same author

Genetic resonance in the p53 signaling network.

Cell systems·2026
Same author

DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.

Cell reports·2025
Same author

Decoding the Central Dogma: Quantitative Insights into Transcription and Translation Dynamics in the p53-Mediated DNA Damage Response.

Journal of molecular biology·2025
Same author

Exploring engagement patterns within a mobile health intervention for women at risk of gestational diabetes.

Women's health (London, England)·2025
Same journal

Mechanisms underpinning chromosome structure in metazoans.

Molecular biology of the cell·2026
Same journal

Conserved and Divergent Modes of Substrate Interaction Define Selective Localizations and Functions of a Cdc14 Phosphatase.

Molecular biology of the cell·2026
Same journal

Dimerization of the centriolin-like protein Nud1 governs spindle pole body inheritance in budding yeast.

Molecular biology of the cell·2026
Same journal

Non-muscle Myosin II acts as a negative feedback mediator to control cell contraction dynamics in adherent cells.

Molecular biology of the cell·2026
Same journal

The tetraspanin disc proteins, peripherin-2 and ROM1, facilitate CNG channel localization to the rod outer segment.

Molecular biology of the cell·2026
Same journal

Csf1 facilitates adaptive membrane lipid remodeling linked to ER-plasma membrane contact sites.

Molecular biology of the cell·2026
See all related articles

Related Experiment Video

Updated: May 16, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

14.1K

Cell confluency affects p53 dynamics in response to DNA damage.

Alina Simerzin1, Emily E Ackerman1, Kotaro Fujimaki1

  • 1Department of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115.

Molecular Biology of the Cell
|April 9, 2025
PubMed
Summary
This summary is machine-generated.

Tumor suppressor protein p53 dynamics were studied in vivo using fluorescent reporters in breast tumors. Most cells showed a single p53 pulse, differing from cultured cells, with low Wip1 levels contributing to this response.

More Related Videos

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

9.9K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K

Related Experiment Videos

Last Updated: May 16, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

14.1K
Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

9.9K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Biophysics

Background:

  • The tumor suppressor protein p53 is crucial for DNA damage response.
  • p53 exhibits oscillations in cultured cells following DNA double-strand breaks (DSB), influencing gene expression and cell fate.
  • In vivo p53 dynamics have been limited to fixed tissues or transcriptional reporters.

Purpose of the Study:

  • To quantify p53 protein level dynamics in vivo in response to DSB.
  • To investigate the impact of cell confluency on p53 dynamics.
  • To identify molecular mechanisms underlying observed p53 dynamics.

Main Methods:

  • Established breast tumor models with a fluorescent p53 reporter.
  • Utilized intravital imaging to monitor p53 dynamics in live animals.
  • Employed live-cell imaging, mathematical modeling, and sensitivity analysis.

Main Results:

  • Observed significant heterogeneity in p53 dynamics among individual cells in vivo.
  • Found that most cells displayed a single, prolonged p53 pulse rather than oscillations.
  • Demonstrated that highly confluent cultured cells also exhibit a single broad p53 pulse.
  • Identified low Wip1 phosphatase levels as a key factor driving these dynamics.

Conclusions:

  • Cell confluency significantly alters p53 dynamics, making them more similar to in vivo conditions.
  • Low Wip1 levels contribute to the single p53 pulse observed in confluent cells.
  • These findings have implications for understanding cancer therapy responses in the tumor microenvironment.