Related Experiment Video

Updated: Jun 5, 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

F-box protein 10, an NF-κB-dependent anti-apoptotic protein, regulates TRAIL-induced apoptosis through modulating

R Ge1, Z Wang, Q Zeng

  • 1Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Cell Death and Differentiation
|January 22, 2011
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in cancer can be overcome by targeting FBXL10. This study reveals FBXL10 as an anti-apoptotic molecule that silences c-Fos, promoting cancer cell survival against TRAIL therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cancer cell death but resistance is a challenge.
  • Activating transcription factor 3 (ATF3) and activating transcription factor 4 (ATF4) are stress-inducible transcription factors.
  • F-box protein 10 (FBXL10) has been implicated in regulating AP-1 family proteins, but its role in apoptosis is unclear.

Purpose of the Study:

  • Investigate the role of FBXL10 in mediating resistance to TRAIL-induced apoptosis.
  • Elucidate the molecular mechanisms by which FBXL10 affects apoptotic pathways.
  • Identify potential therapeutic strategies to overcome TRAIL resistance in cancer.

Main Methods:

  • Western blotting to assess protein levels.
  • Luciferase reporter assays to study transcriptional activity.
  • Quantitative real-time PCR to measure gene expression.
  • Chromatin immunoprecipitation to analyze protein-DNA interactions.
  • Cell viability assays to evaluate apoptosis.

Main Results:

  • FBXL10 acts as a transcriptional repressor of c-Fos, a key apoptosis regulator.
  • FBXL10 expression is regulated by NF-κB-p65 and contributes to TRAIL resistance.
  • Silencing FBXL10 sensitizes resistant cancer cells to TRAIL, while its overexpression promotes resistance.
  • FBXL10 indirectly modulates c-FLIP(L) levels through c-Fos-dependent pathways.
  • TRAIL and proteasome inhibitors downregulate FBXL10 by inhibiting NF-κB signaling.

Conclusions:

  • FBXL10 is a novel anti-apoptotic molecule that promotes cancer cell resistance to TRAIL.
  • A new apoptotic pathway involving NF-κB/FBXL10/c-Fos/c-FLIP is identified.
  • Targeting FBXL10 presents a promising strategy to enhance the efficacy of TRAIL-based cancer therapies.

More Related Videos

Examining BCL-2 Family Function with Large Unilamellar Vesicles08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

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 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...
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...
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...
NF-kB-dependent Signaling Pathway02:26

NF-kB-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...
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.