Related Experiment Video
Updated: Jun 6, 2025
07:42
Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
17.4K
Cytoplasmic HMGB2 orchestrates CALR translocation in the course of immunogenic cell death
Peng Liu1,2, Liwei Zhao1,2, Oliver Kepp1,2
1Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Oncoimmunology
|November 25, 2024
Abstract:
A recent in vitro study showed that pharmacological inhibition of the nuclear export receptor XPO1 suppresses oxaliplatin-induced nuclear release of HMGB1 and HMGB2, as well as the translocation of CALR to the plasma membrane. Moreover, cell-targeted-HMGB2 protein potently induced CALR exposure, even in the absence of oxaliplatin.
Insights
Pharmacological inhibition of XPO1 blocks oxaliplatin
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Oxaliplatin is a common chemotherapy agent.
- Nuclear export receptor XPO1 plays a role in cellular processes.
- High-mobility group box proteins (HMGB1, HMGB2) and Calreticulin (CALR) are involved in cellular responses to chemotherapy.
Purpose of the Study:
- To investigate the role of XPO1 in oxaliplatin-induced cellular events.
- To determine the effect of XPO1 inhibition on HMGB1, HMGB2, and CALR.
- To explore the potential of HMGB2 in inducing CALR exposure.
Main Methods:
- In vitro study design.
- Pharmacological inhibition of XPO1.
- Assessment of nuclear release of HMGB1 and HMGB2.
- Evaluation of CALR translocation to the plasma membrane.
- Cell-targeted HMGB2 protein administration.
Main Results:
- XPO1 inhibition suppressed oxaliplatin-induced nuclear release of HMGB1 and HMGB2.
- XPO1 inhibition prevented oxaliplatin-induced CALR translocation to the plasma membrane.
- Cell-targeted HMGB2 protein induced CALR exposure independently of oxaliplatin.
Conclusions:
- XPO1 is a key mediator in oxaliplatin's effects on HMGB1, HMGB2, and CALR.
- Targeting XPO1 may offer a strategy to modulate chemotherapy-induced cellular responses.
- HMGB2 protein has the potential to induce CALR exposure, suggesting a novel therapeutic avenue.
Related Concept Videos
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
01:30Overview of Cell Death
7.1K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.1K
01:17The Extrinsic Apoptotic Pathway
6.3K
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...
6.3K
01:18Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
01:17Phagocytosis of Apoptotic Cells
3.7K
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...
Normal cells contain receptors that prevent them from being recognized...
3.7K
01:32Export of Misfolded Proteins out of the ER
3.5K
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...
3.5K