Related Experiment Video

Updated: Jun 24, 2026

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

A tumor suppressor function for caspase-2

Lien Ha Ho1, Robyn Taylor, Loretta Dorstyn

  • 1Centre for Cancer Biology, Hanson Institute, Frome Road, Adelaide, SA 5000, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|March 13, 2009
PubMed

Insights

Caspase-2 deficiency enhances cell proliferation and tumor growth in mice. Loss of caspase-2 function also increases resistance to apoptosis, indicating its role as a tumor suppressor protein.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
  • The caspase family of proteases executes apoptosis by cleaving cellular substrates.
  • Caspase-2, despite its evolutionary conservation, has an unclear physiological role, as caspase-2-deficient mice are viable.

Purpose of the Study:

  • To investigate the physiological function of caspase-2.
  • To determine if caspase-2 deficiency influences cell proliferation and tumor development.
  • To elucidate the role of caspase-2 in apoptosis and cell-cycle regulation.

Main Methods:

  • Generation and analysis of caspase-2-deficient mouse embryonic fibroblasts (MEFs).
  • Transformation of MEFs with oncogenes (E1A and Ras) and assessment of tumor formation in nude mice.
  • Evaluation of tumorigenesis in the Emu-Myc lymphoma mouse model.
  • Assessment of apoptosis resistance to chemotherapeutic drugs and DNA damage.
  • Analysis of cell-cycle regulation and response to gamma-irradiation in caspase-2(-/-) MEFs.

Main Results:

  • Caspase-2-deficient MEFs exhibited increased proliferation.
  • Transformed caspase-2(-/-) MEFs formed more aggressive tumors faster than controls.
  • Loss of caspase-2 alleles accelerated lymphomagenesis in the Emu-Myc model.
  • Caspase-2-deficient cells were resistant to drug-induced and DNA damage-induced apoptosis.
  • Caspase-2(-/-) MEFs displayed defective apoptotic responses to cell-cycle checkpoints and abnormal cell cycling post-irradiation.

Conclusions:

  • Loss of caspase-2 function promotes cellular transformation and malignancy.
  • Caspase-2 acts as a tumor suppressor protein, inhibiting tumor development.
  • Caspase-2 plays a critical role in maintaining genomic stability and preventing cancer progression.

More Related Videos

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

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.
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...