Related Experiment Video

Updated: Jul 15, 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

Bid is cleaved upstream of caspase-8 activation during TRAIL-mediated apoptosis in human osteosarcoma cells

Theodore O Garnett1, Maria Filippova, Penelope Jayne Duerksen-Hughes

  • 1Department of Biochemistry and Microbiology, Loma Linda University School of Medicine, 11085 Campus Street, 121 Mortensen Hall, Loma Linda, CA, 92354, USA.

Apoptosis : an International Journal on Programmed Cell Death
|April 14, 2007
PubMed

Insights

Human papillomavirus (HPV) 16 E6 protein differentially affects TRAIL-induced apoptosis. In U2OS cells, TRAIL activates a pathway dependent on Bid, independent of FADD and caspase-8.

Area of Science:

  • Cell biology
  • Molecular biology
  • Cancer research

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells.
  • The human papillomavirus (HPV) 16 E6 protein is studied for its role in cellular pathways.

Purpose of the Study:

  • To investigate the role of HPV 16 E6 in TRAIL-induced apoptosis.
  • To elucidate the molecular mechanisms of TRAIL signaling in HCT116 and U2OS cells.

Main Methods:

  • Utilized HPV 16 E6 protein as a molecular probe.
  • Employed small interfering RNA (siRNA) to silence FADD, procaspase-8, and Bid.
  • Assessed apoptosis induction via TRAIL and anti-DR5 antibodies.
  • Measured cathepsin B activity and inhibition using CA074Me.

Main Results:

  • HPV 16 E6 protected HCT116 cells from TRAIL but not U2OS cells.
  • TRAIL-induced apoptosis in E6-expressing U2OS cells was independent of FADD and caspase-8.
  • Silencing Bid conferred protection from TRAIL, with Bid cleavage preceding caspase-8 activation.
  • TRAIL activated cathepsin B, which was inhibited by CA074Me, affecting apoptosis and Bid cleavage.

Conclusions:

  • TRAIL signaling in U2OS cells involves a Bid-dependent pathway.
  • This pathway is largely independent of FADD and caspase-8.
  • Cathepsin B plays a significant role in TRAIL-mediated apoptosis in these cells.

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 Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

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

Published on: August 2, 2021

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.
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.
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.