Related Experiment Video

Updated: May 25, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX

Ryan E Henry1, Zdenek Andrysik, Ramiro París

  • 1Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, The University of Colorado, Boulder, CO 80309-0347, USA.

The EMBO Journal
|January 17, 2012
PubMed

Insights

p53 activation triggers cell death or arrest. The study reveals p53-dependent DR4 death receptor activation and caspase 8 signaling differentiate apoptotic cells from those arresting, impacting cancer therapy development.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Cellular responses to p53 activation are stimulus- and cell type-dependent.
  • Understanding these mechanisms is crucial for developing p53-based cancer therapies.
  • Gene networks controlling cellular behavior are fundamental to cell fate decisions.

Purpose of the Study:

  • To discover a novel mechanism determining cell fate (proliferation arrest vs. cell death) after p53 activation.
  • To differentiate molecular events leading to arrest versus apoptosis.
  • To elucidate the role of specific pathways in p53-mediated cell fate.

Main Methods:

  • Utilized an experimental system with non-genotoxic and genotoxic agents to elicit stimulus-specific p53 responses.
  • Analyzed the activation of cell-cycle arrest and apoptosis mediators (p21, 14-3-3σ, PUMA, BAX).
  • Investigated mitochondrial translocation of apoptosis mediators and caspase activation.

Main Results:

  • Key apoptosis and cell-cycle arrest mediators were equally activated irrespective of cell fate.
  • Arresting cells showed mitochondrial translocation of PUMA and BAX but no cytochrome C release or caspase activation.
  • Apoptotic cells exhibited p53-dependent DR4 death receptor pathway activation, caspase 8-mediated BID cleavage, and BID-dependent BAX activation.

Conclusions:

  • A novel mechanism involving the DR4 death receptor pathway and extrinsic apoptosis signaling dictates cell fate after p53 activation.
  • The extrinsic apoptotic pathway plays a critical, previously unappreciated role in p53-mediated cell fate decisions.
  • Findings offer insights into developing targeted cancer therapies by modulating p53-induced cell death.

More Related Videos

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.