| Bcl-xL overexpression inhibits taxol-induced Yama protease activity and apoptosis. | |
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MedLine Citation:
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PMID: 8853905 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intracellularly, the anticancer drug taxol induces tubulin polymerization and mitotic arrest, followed by apoptosis. The DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and lamins are known to be degraded during apoptosis. PARP is a substrate for the Yama protease, which is encoded by the CPP32 beta/ Yama gene, whereas lamins are degraded by the Yama and lamin proteases. In the present studies, we determined the effects of enforced overexpression of the antiapoptosis Bcl-xL protein on taxol-mediated microtubule and cell cycle perturbations, as well as on taxol-induced apoptosis and associated Yama protease activity in human myeloid leukemia HL-60 cells. Our data demonstrate that high Bcl-xL levels do not affect the microtubular bundling or mitotic arrest due to taxol but significantly inhibit the morphological, flow cytometric, and DNA fragmentation features associated with taxol-induced apoptosis. This resulted in a significant improvement in the survival of taxol-treated cells that possess high Bcl-xL levels. In the control HL-60 cells, following taxol treatment, whereas the mRNA of Yama was not induced, taxol-induced apoptosis was associated with Yama activation and PARP as well as lamin B1 degradation. These features were blocked by coculture of these cells with the cysteine protease inhibitor YVAD-cmk as well as in cells with overexpression of Bcl-xL. These results suggest that Bcl-xL antagonizes taxol-induced apoptosis by a mechanism that interferes with the activation of a key protease involved in the execution of apoptosis. |
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Authors:
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A M Ibrado; Y Huang; G Fang; K Bhalla |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Volume: 7 ISSN: 1044-9523 ISO Abbreviation: Cell Growth Differ. Publication Date: 1996 Aug |
Date Detail:
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Created Date: 1997-02-26 Completed Date: 1997-02-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9100024 Medline TA: Cell Growth Differ Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1087-94 Citation Subset: IM |
Affiliation:
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Department of Medicine, Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology* Blotting, Northern Blotting, Western Caspase 3 Caspases* Cysteine Endopeptidases / biosynthesis* DNA Fragmentation / physiology Humans Lamin Type B* Lamins Membrane Proteins / drug effects, genetics Microtubules / physiology Mitosis / physiology Nuclear Proteins / drug effects Paclitaxel / pharmacology* Poly(ADP-ribose) Polymerases / drug effects Proto-Oncogene Proteins / biosynthesis*, drug effects, genetics Proto-Oncogene Proteins c-bcl-2 / drug effects, genetics Transfection Tumor Cells, Cultured bcl-2 Homologous Antagonist-Killer Protein bcl-2-Associated X Protein bcl-X Protein |
| Grant Support | |
ID/Acronym/Agency:
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CA56613/CA/NCI NIH HHS; CA63382/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/BAK1 protein, human; 0/BCL2L1 protein, human; 0/Lamin Type B; 0/Lamins; 0/Membrane Proteins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 0/lamin B1; 33069-62-4/Paclitaxel; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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