Related Experiment Video

Updated: Jun 19, 2026

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates
11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Published on: March 31, 2012

Impaired TNFalpha-induced A20 expression in E1A/Ras-transformed cells

H-L Huang1, W-C Yeh, M-Z Lai

  • 1The Campbell Family Institute of Breast Cancer Research, Ontario Cancer Institute, University Health Network and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada. hhuang@mail.cjcu.edu.tw

British Journal of Cancer
|October 15, 2009
PubMed
Abstract

Insights

Tumour necrosis factor (TNF) can kill transformed cells, but survival signals often protect them. This study found that impaired A20 induction in E1A/Ras-transformed cells makes them sensitive to TNF-induced apoptosis.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Apoptosis research

Background:

  • Tumour necrosis factor (TNF) triggers cell death pathways and can eliminate transformed cells.
  • However, TNF also activates survival signals, like NF-kappaB, which promote anti-apoptotic gene expression and protect cells from TNF-induced toxicity.

Purpose of the Study:

  • To investigate the factors determining TNF sensitivity in transformed cells.
  • To compare TNF-induced apoptosis in wild-type and E1A/Ras-transformed mouse embryonic fibroblasts (MEFs).

Main Methods:

  • Compared TNF-induced apoptosis in wild-type and E1A/Ras-transformed MEFs.
  • Analyzed TNF signaling pathways, including NF-kappaB, A20 induction, p53 stabilization, and p38/JNK signaling.
  • Assessed A20 promoter activity and the role of Bcl-3 in E1A/Ras MEFs.

Main Results:

  • E1A/Ras-transformed MEFs, unlike wild-type MEFs, were susceptible to TNF-induced apoptosis.
  • A20 induction was abolished in E1A/Ras-transformed cells despite intact NF-kappaB signaling.
  • Reintroducing A20 rescued these cells from TNF-induced death and reduced FADD/caspase-8 complex formation.

Conclusions:

  • Impaired induction of the survival factor A20 is a key determinant of TNF sensitivity in E1A/Ras-transformed cells.
  • Targeting specific survival factors like A20 could be a strategy to enhance TNF-induced apoptosis in cancer therapy.

More Related Videos

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact11:29

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact

Published on: July 17, 2016

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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...