Related Experiment Video

Updated: Jul 17, 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

Essential postmitochondrial function of p53 uncovered in DNA damage-induced apoptosis in neurons

A E Vaughn1, M Deshmukh

  • 1Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

Cell Death and Differentiation
|January 16, 2007
PubMed

Insights

DNA damage triggers apoptosis in neurons differently than NGF deprivation. p53 protein is crucial for inactivating XIAP, enabling caspase activation and cell death following DNA damage.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Apoptosis Research

Background:

  • Apoptosis in postmitotic sympathetic neurons requires overcoming X-linked inhibitor of apoptosis protein (XIAP) inhibition of caspases.
  • Two distinct pathways exist for XIAP inactivation: one following nerve growth factor (NGF) deprivation and another following DNA damage.

Purpose of the Study:

  • To elucidate the mechanism of XIAP inactivation in neurons subsequent to DNA damage.
  • To compare this mechanism with XIAP inactivation following NGF deprivation.

Main Methods:

  • Investigated XIAP inactivation mechanisms in postmitotic sympathetic neurons.
  • Utilized p53-deficient neurons to assess the role of p53 in XIAP regulation.
  • Examined the impact of Apaf-1 induction on XIAP inactivation and caspase activation.

Main Results:

  • DNA damage-induced XIAP inactivation occurs via a p53-mediated induction of Apaf-1, distinct from NGF deprivation-induced degradation.
  • p53-deficient neurons resist XIAP inactivation and cytochrome c release after DNA damage.
  • Restoring Apaf-1 induction in p53-deficient neurons sensitizes them to cytochrome c, overcoming XIAP inhibition.

Conclusions:

  • p53 plays an essential role in regulating caspase activation downstream of mitochondria following DNA damage in neurons.
  • This study reveals a novel function for p53 in controlling apoptosis execution in neurons, beyond its known role upstream of cytochrome c release.

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

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

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...
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...
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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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.