Related Experiment Video

Updated: Sep 23, 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

p53-induced inhibition of protein synthesis is independent of apoptosis

Constantina Constantinou1, Martin Bushell, Ian W Jeffrey

  • 1Translational Control Group, Department of Basic Medical Sciences, St George's Hospital Medical School, Cranmer Terrace, London, UK.

European Journal of Biochemistry
|July 19, 2003
PubMed

Insights

Activating p53 rapidly halts protein synthesis by cleaving translation factors, a process independent of caspases and apoptosis. This early inhibition of protein synthesis precedes cell death, offering new insights into p53

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor protein p53 plays a critical role in cellular responses to stress.
  • p53 activation can lead to cell cycle arrest, apoptosis, and metabolic changes.
  • Protein synthesis regulation is crucial for cellular function and survival.

Purpose of the Study:

  • To investigate the impact of activated p53 on protein synthesis in murine erythroleukaemia cells.
  • To determine the role of caspases in p53-mediated translational inhibition.
  • To elucidate the relationship between p53-induced protein synthesis inhibition and apoptosis.

Main Methods:

  • Activation of a temperature-sensitive p53 in murine erythroleukaemia cells.
  • Analysis of protein synthesis rates and cleavage of translation initiation factors (eIF4GI, eIF4B).
  • Assessment of caspase activity and the effects of caspase inhibitors (z-VAD.FMK) and erythropoietin.

Main Results:

  • p53 activation caused rapid inhibition of protein synthesis, preceding cell proliferation arrest and death.
  • Specific cleavages of translation initiation factors eIF4GI and eIF4B were observed.
  • These translational effects and factor cleavages were resistant to caspase inhibition and could be dissociated from apoptosis.

Conclusions:

  • p53-regulated cleavages of eIF4GI and eIF4B are caspase-independent events.
  • Inhibition of protein synthesis by p53 can be dissociated from the induction of apoptosis.
  • These findings reveal a novel, caspase-independent mechanism by which p53 regulates translation.

More Related Videos

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

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...