Related Experiment Video

Updated: Sep 26, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Mutant p53 can delay growth arrest and loss of CDK2 activity in senescing human fibroblasts without reducing

Fiona Wyllie1, Michele Haughton, Jiri Bartek

  • 1Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom. wyllie@cf.ac.uk

Experimental Cell Research
|April 23, 2003
PubMed

Insights

Functional wild-type p53 is essential for cellular senescence. This study reveals that p53-mediated senescence involves factors beyond p21, impacting cyclin E-cdk2 complex formation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Functional wild-type p53 protein is crucial for initiating replicative senescence in human diploid fibroblasts (HDF).
  • Abrogating p53 function or down-regulating its effector p21 extends HDF lifespan, but p21 reduction isn't always necessary for lifespan extension.

Purpose of the Study:

  • To investigate how p53 function abrogation overcomes senescence independently of p21 levels.
  • To explore the mechanisms by which p53 influences senescence beyond p21 modulation.

Main Methods:

  • Expression of dominant-negative mutant p53 (143(ala)) in HDF.
  • Analysis of cyclin-dependent kinase 2 (cdk2) protein levels and p21-free cdk2.
  • Assessment of retinoblastoma protein phosphorylation.
  • Forced overexpression of cdk2 in near-senescent HDF.

Main Results:

  • HDF expressing 143(ala) mutant p53 showed increased cdk2 protein and p21-free cdk2 compared to senescent cells.
  • Active cyclin E-cdk2 complexes capable of phosphorylating the retinoblastoma protein were formed.
  • Forced cdk2 overexpression did not restore cdk2-associated kinase activity in near-senescent HDF.

Conclusions:

  • p53-mediated cellular senescence is regulated by factors other than p21.
  • These factors modulate the formation of cyclin E-cdk2 complexes, influencing cell cycle progression and senescence entry.

More Related Videos

Senescence Detection Using Reflected Light in Adipose Stromal Vascular Fraction10:08

Senescence Detection Using Reflected Light in Adipose Stromal Vascular Fraction

Published on: June 5, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Related Concept Videos

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...
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...
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...
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...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...