Related Experiment Video

Updated: Jun 13, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response

P Pawlikowska1, I Leray, B de Laval

  • 1INSERM U, Institut Cochin, Paris, France.

Cell Death and Differentiation
|May 15, 2010
PubMed

Insights

The early-response gene IEX-1 controls Mcl-1 nuclear accumulation after DNA damage. This interaction is crucial for maintaining genomic stability and checkpoint arrest, offering potential cancer therapy targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The early-response gene product IEX-1 (IER3) interacts with the anti-apoptotic protein Mcl-1.
  • Mcl-1 is a member of the Bcl-2 family, known for its role in preventing apoptosis.

Purpose of the Study:

  • To investigate the functional interaction between IEX-1 and Mcl-1 in response to DNA damage.
  • To elucidate the role of this interaction in maintaining genomic stability and cellular response to genotoxic stress.

Main Methods:

  • γ-irradiation and genotoxic agents were used to induce DNA damage.
  • Western blotting and immunofluorescence were employed to track protein localization and levels.
  • Ataxia telangiectasia mutated (ATM) activity was assessed.
  • Cellular sensitivity to genotoxic and replicative stresses was evaluated.
  • Chk1 activation and G2 checkpoint arrest were monitored.

Main Results:

  • IEX-1 is rapidly induced by DNA damage in an ATM-dependent manner.
  • IEX-1 is essential for Mcl-1 nuclear translocation following DNA damage.
  • Proteasomal degradation of IEX-1 facilitates Mcl-1 return to the cytosol.
  • Loss of IEX-1 or Mcl-1 results in genomic instability and increased stress sensitivity.
  • IEX-1 and Mcl-1 cooperate to maintain Chk1 activation and G2 checkpoint arrest.

Conclusions:

  • The IEX-1/Mcl-1 interaction is a key regulator of the DNA damage response.
  • Mcl-1 nuclear translocation enhances tumor resistance to DNA damage-based therapies.
  • Targeting IEX-1 degradation pathways may sensitize tumor cells to chemotherapy.

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview