Prevalent Loss of Mitotic Spindle Checkpoint in Adult T-cell Leukemia Confers Resistance to Microtubule Inhibitors
| Autor: | Kuan-Teh Jeang, Yoichi Iwanaga, Takefumi Kasai, Hidekatsu Iha |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cytoplasm
Leukemia T-Cell Time Factors Cell Survival viruses T-cell leukemia Mitosis Antineoplastic Agents Apoptosis Spindle Apparatus Biology Microtubules Biochemistry Jurkat cells Cell Line Jurkat Cells chemistry.chemical_compound Piperidines immune system diseases hemic and lymphatic diseases Humans Enzyme Inhibitors Molecular Biology Cell Line Transformed Cell Nucleus Flavonoids Human T-lymphotropic virus 1 Dose-Response Relationship Drug Nocodazole hemic and immune systems Cell Biology G2-M DNA damage checkpoint Mitotic spindle checkpoint Cell biology Spindle checkpoint Phenotype Mitotic spindle assembly checkpoint chemistry HeLa Cells Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 277:5187-5193 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110295200 |
| Popis: | Human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL). Molecularly, ATL cells have extensive aneugenic abnormalities that occur, at least in part, from cell cycle dysregulation by the HTLV-I-encoded Tax oncoprotein. Here, we compared six HTLV-I-transformed cells to Jurkat and primary peripheral blood mononuclear cells (PBMC) in their responses to treatment with microtubule inhibitors. We found that both Jurkat and PBMCs arrested efficiently in mitosis when treated with nocodazole. By contrast, all six HTLV-I cells failed to arrest comparably in mitosis, suggesting that ATL cells have a defect in the mitotic spindle assembly checkpoint. Mechanistically, we observed that in HTLV-I Tax-expressing cells human spindle assembly checkpoint factors hsMAD1 and hsMAD2 were mislocated from the nucleus to the cytoplasm. This altered localization of hsMAD1 and hsMAD2 correlated with loss of mitotic checkpoint function and chemoresistance to microtubule inhibitors. |
| Databáze: | OpenAIRE |
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