Related Experiment Video

Updated: Aug 19, 2026

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity
04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Fas-associated factor-1 mediates chemotherapeutic-induced apoptosis via death effector filament formation

Min-Young Park1, Seung-Wook Ryu, Kwang Dong Kim

  • 1Research Center for Biomedicinal Resources and Department of Genetic Engineering, PaiChai University, Daejeon, Korea.

International Journal of Cancer
|February 3, 2005
PubMed

Insights

Fas-associated factor-1 (FAF1) enhances chemotherapy effectiveness by promoting the formation of death effector filaments (DEF), crucial for programmed cell death. Reduced FAF1 levels in gastric cancer highlight its potential role in treatment resistance.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Fas-associated factor-1 (FAF1) is implicated in Fas-mediated apoptosis and its levels are reduced in gastric carcinomas.
  • Understanding FAF1's role in apoptosis is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the mechanism by which FAF1 mediates chemotherapeutic-induced apoptosis.
  • To elucidate FAF1's role in the formation of death effector filaments (DEF).

Main Methods:

  • Overexpression and antisense FAF1 constructs were used in cancer cells.
  • Cells were treated with chemotherapeutics like staurosporine (STS), cisplatin (CDDP), and etoposide (VP16).
  • DEF assembly was analyzed using confocal microscopy, and FAF1 truncates were employed to identify functional domains.

Main Results:

  • FAF1 overexpression enhanced DEF assembly and apoptosis induced by STS, CDDP, and VP16.
  • FAF1 sensitized cells to chemotherapeutics in a dose- and time-dependent manner.
  • The FAF1 domain interacting with FADD and caspase-8 was sufficient for enhancing DEF assembly, with FAF1, FADD, and caspase-8 co-localizing in DEFs.

Conclusions:

  • FAF1 mediates chemotherapeutic-induced apoptosis through its role in DEF assembly.
  • FAF1 acts as a molecular mechanism for chemosensitization, offering potential therapeutic targets for gastric cancer.

More Related Videos

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

Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells13:53

Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells

Published on: August 26, 2021

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.
Actin Filament Depolymerization01:19

Actin Filament Depolymerization

Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
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.
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...