1. Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis.
- Author
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Yuan TT, Huang Y, Zhou CX, Yu Y, Wang LS, Zhuang HY, and Chen GQ
- Subjects
- Amino Acid Sequence, Camptothecin analogs & derivatives, Camptothecin pharmacology, Caspase 3 metabolism, Cell Line, Tumor, Cell Nucleus drug effects, Dose-Response Relationship, Drug, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum enzymology, Endoplasmic Reticulum pathology, Enzyme Activation drug effects, Etoposide pharmacology, Humans, Leukemia enzymology, Leukemia pathology, Methotrexate pharmacology, Microtubules drug effects, Molecular Sequence Data, Neoplasm Proteins analysis, Neoplasm Proteins chemistry, Protein Transport drug effects, Apoptosis drug effects, Cell Nucleus enzymology, DNA Damage, Tetrahydrofolate Dehydrogenase metabolism
- Abstract
Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA. By applying subcellular proteomic analysis, we identified that the DHFR protein was translocated from cytoplasm into the nucleus when apoptosis was induced by NSC606985, a camptothecin analogue. The nuclear translocation of DHFR protein during apoptosis was independent of the cellular context, but it was more sensitive in cell death induction by DNA damaging agents such as doxorubicin, etoposide and ultraviolent radiation than endoplasmic reticulum stressors (brefeldin-A and tunicamycin) and anti-microtubule agents (paclitaxel and nocodozole). The addition of methotrexate almost completely blocked the nuclear translocation of DHFR protein. Further investigations showed that the nuclear translocation of DHFR was not a pre-requisite for DNA damage induced apoptosis. Therefore, its potential biological significance remains to be further explored.
- Published
- 2009
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