Related Experiment Video

Updated: Jul 4, 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

Nuclear trafficking of pro-apoptotic kinases in response to DNA damage

Kiyotsugu Yoshida1

  • 1Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan. yos.mgen@mri.tmd.ac.jp

Trends in Molecular Medicine
|June 10, 2008
PubMed

Insights

Cellular responses to DNA damage involve complex signaling pathways. Nuclear localization of pro-apoptotic kinases is a key mechanism regulating cell fate and apoptosis induction, offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cellular response to genotoxic stress involves cell-cycle arrest, DNA repair, and apoptosis.
  • Signals determining cell fate after DNA damage are not fully understood.
  • Pro-apoptotic kinases like PKCdelta, c-Abl, and DYRK2 shuttle between nucleus and cytoplasm upon DNA damage.

Purpose of the Study:

  • To review recent findings on kinase nuclear targeting in response to DNA damage.
  • To highlight the role of kinase localization in apoptosis induction.
  • To discuss potential therapeutic implications of this regulatory mechanism.

Main Methods:

  • Literature review of studies on kinase shuttling and DNA damage response.
  • Analysis of mechanisms regulating nuclear-cytoplasmic transport of pro-apoptotic kinases.
  • Discussion of the functional consequences of kinase localization on apoptosis.

Main Results:

  • Nuclear-cytoplasmic shuttling of specific pro-apoptotic kinases is a conserved response to DNA damage.
  • Kinase localization is crucial for their pro-apoptotic function.
  • The precise regulation of this shuttling mechanism requires further investigation.

Conclusions:

  • Nuclear targeting of kinases is a novel and essential regulatory mechanism in DNA damage-induced apoptosis.
  • Understanding kinase localization offers insights into cell fate determination.
  • This mechanism presents potential targets for novel therapeutic strategies.

More Related Videos

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

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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...
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...
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...
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.