Related Experiment Video
Updated: Jun 24, 2026
10:12
Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
Published on: June 14, 2024
ATM blocks tunicamycin-induced endoplasmic reticulum stress
Long He1, Sun Ok Kim, Osong Kwon
1Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon 305-806, Republic of Korea.
FEBS Letters
|March 24, 2009
Summary
The ataxia telangiectasia mutated (ATM) gene blocks endoplasmic reticulum stress (ER-stress). This finding is crucial for understanding cancer cell proliferation and developing targeted therapies.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Endoplasmic reticulum stress (ER-stress) is implicated in cancer cell proliferation.
- The ataxia telangiectasia mutated (ATM) gene's role in ER-stress is not fully understood.
Purpose of the Study:
- To investigate the role of the ATM gene in blocking ER-stress.
- To elucidate the mechanisms by which ATM influences ER-stress signaling pathways.
Main Methods:
- Utilized Atm-deficient AT5BIVA fibroblasts and wild-type ATM-transfected cells.
- Induced ER-stress using tunicamycin and ionizing radiation (IR).
- Assessed ER-stress markers including X-box protein-1 (XBP-1) splicing, GRP78 expression, and caspase activation via Western blotting and RT-PCR.
Main Results:
- Tunicamycin or IR increased ER-stress markers in Atm-deficient cells.
- Wild-type ATM expression significantly reduced tunicamycin-induced caspase activation.
- ATM knockdown exacerbated ER-stress and increased sensitivity to tunicamycin.
Conclusions:
- ATM acts as a critical suppressor of ER-stress.
- ATM signaling is a key regulator of ER-stress pathways relevant to cancer proliferation.
- Targeting ATM may offer therapeutic strategies for managing ER-stress in cancer.
Related Concept Videos
01:17Role of ER in the Secretory Pathway
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:31Regulation 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...
01:32Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
01:23Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
01:30The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...