Related Experiment Video

Updated: Jun 2, 2026

In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening
08:16

In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening

Published on: October 6, 2022

Fanconi anemia D2 protein is an apoptotic target mediated by caspases

Su-Jung Park1, Brian D Beck, M Reza Saadatzadeh

  • 1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Journal of Cellular Biochemistry
|April 27, 2011
PubMed

Insights

DNA damage triggers the disappearance of FANCD2 protein, a key DNA repair factor. This process is mediated by caspases, indicating FANCD2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • DNA Damage Response

Background:

  • FANCD2 (Fanconi anemia complementation group D2) is a crucial protein in the FANC-BRCA1 DNA repair pathway.
  • Monoubiquitination of FANCD2 is a key marker of cellular response to DNA damage.

Purpose of the Study:

  • To investigate the fate of FANCD2 protein and its monoubiquitination status following DNA damage.
  • To determine the pathway responsible for FANCD2 degradation and its potential role as an apoptosis indicator.

Main Methods:

  • Induction of DNA damage and apoptosis using various agents.
  • Monitoring FANCD2 protein levels and monoubiquitination.
  • Treatment with proteasome and caspase inhibitors.
  • Experiments in cells with and without FANCA.

Main Results:

  • DNA damage induced dose-dependent disappearance of FANCD2 protein.
  • FANCD2 degradation correlated with BRCA1 and PARP degradation, suggesting caspase involvement.
  • FANCD2 disappearance was blocked by caspase inhibitors but not proteasome inhibitors.
  • FANCD2 disappearance occurred independently of the FANC-BRCA1 pathway and monoubiquitination.
  • TNF-α treatment also induced FANCD2 disappearance without monoubiquitination.

Conclusions:

  • FANCD2 is a target of the caspase-mediated apoptotic pathway.
  • The disappearance of FANCD2 is an early indicator of apoptotic cell death.
  • This degradation pathway is independent of the canonical FANC-BRCA1 DNA repair mechanism.

More Related Videos

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

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

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...
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 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.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...