Related Experiment Video
Updated: Jul 13, 2025
13:04
Atomic Absorbance Spectroscopy to Measure Intracellular Zinc Pools in Mammalian Cells
Published on: May 16, 2019
38.7K
Leukemia cells accumulate zinc for oncofusion protein stabilization
Richard Görg1, Anna Büttgenbach1, Jana Jakobs1
1Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
The Journal of Nutritional Biochemistry
|October 15, 2023
Summary
Zinc deficiency degrades oncofusion proteins in leukemia cells, like PML-RARα in acute promyelocytic leukemia (APL) and BCR-ABL1 in chronic myeloid leukemia (CML), by increasing caspase 3 activity and autophagy.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) are hematological malignancies driven by oncofusion proteins.
- Elevated intracellular zinc levels in leukemia cells may stabilize these oncofusion proteins, promoting proliferation.
Purpose of the Study:
- To investigate the role of zinc homeostasis in leukemia cell characteristics.
- To explore potential pathways for degrading oncofusion proteins in leukemia.
Main Methods:
- Flow cytometry to analyze intracellular zinc levels.
- Zinc deficiency and reconstitution experiments in APL (NB4) and CML (K562) cell lines.
- Caspase 3 activity assays and fluorescence microscopy for autophagy analysis.
- Expression analysis of zinc transporters (ZIP2, ZIP10, ZnT3).
Main Results:
- Zinc deficiency induced degradation of PML-RARα and BCR-ABL1 oncofusion proteins.
- Degradation correlated with increased caspase 3 activity and enhanced autophagy (lysosome activity).
- Zinc reconstitution normalized caspase 3 activity and prevented degradation.
- Leukemia cells showed altered expression of zinc transporters and excessive zinc accumulation.
Conclusions:
- Altered zinc homeostasis is crucial for leukemia cell characteristics.
- Zinc deficiency triggers oncofusion protein degradation via caspase 3 activation and autophagy.
- Targeting zinc homeostasis presents a potential strategy for degrading oncofusion proteins in leukemia.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
00:50Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K