Related Experiment Video

Updated: Aug 22, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

The secretable form of trimeric TRAIL, a potent inducer of apoptosis

Mi-Hyang Kim1, Timothy R Billiar, Dai-Wu Seol

  • 1Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Biochemical and Biophysical Research Communications
|September 11, 2004
PubMed

Insights

Researchers engineered an artificial Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) gene. This novel gene enhances cancer cell apoptosis, offering a promising new avenue for anticancer gene therapy.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cancer Research

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine that induces apoptosis in cancer cells.
  • Soluble recombinant TRAIL shows potential for cancer therapy by limiting tumor growth without harming normal tissues.
  • Existing TRAIL proteins have limitations in efficacy.

Purpose of the Study:

  • To develop an artificial TRAIL gene for enhanced secretion and apoptotic activity.
  • To investigate the potential of this novel gene in anticancer gene therapy.

Main Methods:

  • Constructed an artificial TRAIL gene incorporating a secretion signal, trimerization domain, and apoptosis-inducing moiety.
  • Utilized expression vectors to produce secretable, trimeric TRAIL proteins.
  • Assessed the apoptotic activity of the engineered TRAIL proteins in vitro.

Main Results:

  • The artificial TRAIL gene successfully expressed and secreted trimeric TRAIL into culture supernatant.
  • The secreted trimeric TRAIL proteins exhibited enhanced apoptotic activity compared to conventional TRAIL.
  • Demonstrated increased efficacy in inducing cancer cell apoptosis.

Conclusions:

  • The engineered artificial TRAIL gene holds significant potential for developing novel anticancer therapies.
  • Gene therapy utilizing this artificial TRAIL gene may offer an effective strategy against various cancers.
  • The enhanced apoptotic activity suggests improved therapeutic outcomes.

More Related Videos

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

Related Concept Videos

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...
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...
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.
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.
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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.