Related Experiment Video

Updated: Jul 3, 2026

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data
07:17

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data

Published on: February 7, 2025

TWEAKing death

Jonathan D Ashwell1

  • 1Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jda@pop.nci.nih.gov

The Journal of Cell Biology
|July 9, 2008
PubMed

Insights

Smac mimetics and the cytokine TWEAK induce tumor cell death through similar pathways. Both reduce levels of cellular inhibitor of apoptosis proteins (cIAP1/2), offering potential for cancer therapy.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Immunology

Background:

  • Smac mimetics induce tumor cell death by degrading cellular inhibitor of apoptosis proteins (cIAP1/2), activating NF-κB and TNF signaling.
  • Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a cytokine involved in cell death pathways.

Purpose of the Study:

  • To investigate the similarities between TWEAK-induced and Smac mimetic-induced tumor cell death.
  • To explore the role of cIAP1/2 degradation in these pathways.

Main Methods:

  • Comparative analysis of cell death signaling pathways.
  • Assessment of protein degradation and activation markers.

Main Results:

  • TWEAK and Smac mimetics trigger tumor cell death through remarkably similar events.
  • A common, necessary feature is the reduction of cIAP1 and, in some cases, cIAP2 and TNF receptor-associated factor 2.
  • These similarities are also observed in TNF receptor 2 signaling.

Conclusions:

  • Cell death pathways induced by TWEAK and Smac mimetics share common regulatory mechanisms involving cIAP1/2.
  • Induced cIAP deficiency (cIDE) may be a viable strategy for selective elimination of neoplastic cells.

More Related Videos

High-Throughput Behavioral Aging and Lifespan Assays Using the Lifespan Machine08:53

High-Throughput Behavioral Aging and Lifespan Assays Using the Lifespan Machine

Published on: January 26, 2024

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording06:36

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording

Published on: September 1, 2022

Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Kubler Ross's Stages of Dying01:21

Kubler Ross's Stages of Dying

Elisabeth Kübler-Ross significantly advanced psychology's understanding of the process of dying with her influential book, On Death and Dying (1969). She focused on studying terminally ill individuals and outlined five stages commonly experienced when coping with death: denial, anger, bargaining, depression, and acceptance.
In denial, individuals reject the reality of their condition, often thinking, "This isn't true; I feel fine," as a way to protect themselves from emotional distress. Anger...