Related Experiment Video

Updated: Jun 18, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Caspase 2-mediated tumor suppression involves survivin gene silencing

M Guha1, F Xia, C M Raskett

  • 1Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01609, USA.

Oncogene
|November 26, 2009
PubMed

Insights

Caspase 2 suppresses tumors by inhibiting survivin gene transcription through RIP1 cleavage. This blocks NF-kappaB signaling, enhancing apoptosis and preventing cancer growth.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell death pathways

Background:

  • Endogenous tumor suppression opposes aberrant cell survival.
  • The molecular mechanisms underlying tumor suppression are not fully understood.
  • Caspase 2, a death effector, has largely unknown functions.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which caspase 2 contributes to tumor suppression.
  • To investigate the role of caspase 2 in regulating survivin gene transcription.
  • To identify the pathway linking caspase 2 to NF-kappaB signaling and cell survival.

Main Methods:

  • Investigated the effect of caspase 2 on survivin gene expression.
  • Analyzed the interaction between caspase 2 and RIP1.
  • Assessed the impact of RIP1 cleavage on NF-kappaB target genes.
  • Evaluated tumor suppression in vivo.

Main Results:

  • Caspase 2 represses survivin gene transcription.
  • Caspase 2 cleaves the NF-kappaB activator RIP1.
  • Loss of RIP1 abolishes NF-kappaB target gene transcription, including survivin.
  • This leads to deregulated mitotic transitions, enhanced apoptosis, and suppressed tumorigenicity in vivo.

Conclusions:

  • Caspase 2 acts as an endogenous inhibitor of NF-kappaB-dependent cell survival.
  • The caspase 2-RIP1-NF-kappaB pathway is a novel mechanism of tumor suppression.
  • This pathway may contribute to human tumor suppression.

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

Related Concept Videos

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...
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...
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...