Phosphorylation and Proteasome-Dependent Degradation of Bcl-2 in Mitotic-Arrested Cells after Microtubule Damage
Treatment of NIH-OVCAR-3 cells with paclitaxel, a microtubule-stabilizing agent, induces mitotic arrest and apoptosis, but also Bcl-2 phosphorylation. We report here that Bcl-2 phosphorylation precedes Bcl-2 down-regulation and that both events are closely associated with mitotic arrest, but are not...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1999-09, Vol.262 (3), p.823-827 |
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| creator | Chadebech, Philippe Brichese, Laetitia Baldin, Véronique Vidal, Simone Valette, Annie |
| description | Treatment of NIH-OVCAR-3 cells with paclitaxel, a microtubule-stabilizing agent, induces mitotic arrest and apoptosis, but also Bcl-2 phosphorylation. We report here that Bcl-2 phosphorylation precedes Bcl-2 down-regulation and that both events are closely associated with mitotic arrest, but are not sufficient for paclitaxel to trigger apoptosis. Indeed, when paclitaxel-treated cells were induced to exit mitosis in the presence of 2-aminopurine, Bcl-2 phosphorylation and Bcl-2 down-regulation were both inhibited. In contrast, when apoptosis was inhibited by a caspase inhibitor or Bcl-2 over-expression, Bcl-2 phosphorylation and down-regulation still occurred. Furthermore, we show that Bcl-2 is degraded in mitosis by the proteasome-dependent pathway since Bcl-2 down-regulation is inhibited by proteasome inhibitors such as MG132, Lactacystin and LLnL. Taken together these results indicate that mitotic spindle damage results in post-translational modifications of Bcl-2 by phosphorylation and degradation. |
| doi_str_mv | 10.1006/bbrc.1999.1291 |
| format | Article |
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We report here that Bcl-2 phosphorylation precedes Bcl-2 down-regulation and that both events are closely associated with mitotic arrest, but are not sufficient for paclitaxel to trigger apoptosis. Indeed, when paclitaxel-treated cells were induced to exit mitosis in the presence of 2-aminopurine, Bcl-2 phosphorylation and Bcl-2 down-regulation were both inhibited. In contrast, when apoptosis was inhibited by a caspase inhibitor or Bcl-2 over-expression, Bcl-2 phosphorylation and down-regulation still occurred. Furthermore, we show that Bcl-2 is degraded in mitosis by the proteasome-dependent pathway since Bcl-2 down-regulation is inhibited by proteasome inhibitors such as MG132, Lactacystin and LLnL. 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We report here that Bcl-2 phosphorylation precedes Bcl-2 down-regulation and that both events are closely associated with mitotic arrest, but are not sufficient for paclitaxel to trigger apoptosis. Indeed, when paclitaxel-treated cells were induced to exit mitosis in the presence of 2-aminopurine, Bcl-2 phosphorylation and Bcl-2 down-regulation were both inhibited. In contrast, when apoptosis was inhibited by a caspase inhibitor or Bcl-2 over-expression, Bcl-2 phosphorylation and down-regulation still occurred. Furthermore, we show that Bcl-2 is degraded in mitosis by the proteasome-dependent pathway since Bcl-2 down-regulation is inhibited by proteasome inhibitors such as MG132, Lactacystin and LLnL. Taken together these results indicate that mitotic spindle damage results in post-translational modifications of Bcl-2 by phosphorylation and degradation.</description><subject>Acetylcysteine - analogs & derivatives</subject><subject>Acetylcysteine - pharmacology</subject><subject>Amino Acid Chloromethyl Ketones - pharmacology</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biochemistry, Molecular Biology</subject><subject>Cell Behavior</subject><subject>Cellular Biology</subject><subject>Cysteine Endopeptidases - metabolism</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, bcl-2</subject><subject>Humans</subject><subject>Leupeptins - pharmacology</subject><subject>Life Sciences</subject><subject>Microtubules - drug effects</subject><subject>Microtubules - physiology</subject><subject>Mitosis</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Ovarian Neoplasms</subject><subject>Paclitaxel - toxicity</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Santé publique et épidémiologie</subject><subject>Subcellular Processes</subject><subject>Tumor Cells, Cultured</subject><subject>Virulence Factors, Bordetella - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE2P0zAQhi0EYrsLV47IP4CUmdRJ6mNpgUUqYg8gcbP8MdkaJXFkuyvtv19XQWgvnEbyPO-r8cPYO4Q1ArQfjYl2jVLKNdYSX7AVgoSqRhAv2QoKUZXn31fsOqU_AIiila_ZVVl3KECu2Hx3Cmk-hfg46OzDxPXk-F0MmXQKI1UHmmlyNGV-oPuo3QKFnn-yQ1VzP_HvPofsbbWLkVImx_c0DInrPlMsS1u6zuY8ED_oUd_TG_aq10Oit3_nDfv15fPP_W11_PH12353rKzALld607jW9dRJAYaANl1jGrO11EKPfWO6zglyW4u1FeBII5q2B9PUoqOtEN3mhn1Yek96UHP0o46PKmivbndH5adEcVSwqQW2KB-w4OsFL_emFKn_l0FQF9PqYlpdTKuL6RJ4vwTmsxnJPcMXtQXYLgCVXz54iipZT5Ml5yPZrFzw_-t-AphMjkM</recordid><startdate>19990907</startdate><enddate>19990907</enddate><creator>Chadebech, Philippe</creator><creator>Brichese, Laetitia</creator><creator>Baldin, Véronique</creator><creator>Vidal, Simone</creator><creator>Valette, Annie</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0001-8523-0494</orcidid></search><sort><creationdate>19990907</creationdate><title>Phosphorylation and Proteasome-Dependent Degradation of Bcl-2 in Mitotic-Arrested Cells after Microtubule Damage</title><author>Chadebech, Philippe ; Brichese, Laetitia ; Baldin, Véronique ; Vidal, Simone ; Valette, Annie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-a35d6dfe7940be0e375b5b8ce60f1f5b77d4ed8c12c40dea11b6f0b5247e84473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Acetylcysteine - analogs & derivatives</topic><topic>Acetylcysteine - pharmacology</topic><topic>Amino Acid Chloromethyl Ketones - pharmacology</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biochemistry, Molecular Biology</topic><topic>Cell Behavior</topic><topic>Cellular Biology</topic><topic>Cysteine Endopeptidases - metabolism</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, bcl-2</topic><topic>Humans</topic><topic>Leupeptins - pharmacology</topic><topic>Life Sciences</topic><topic>Microtubules - drug effects</topic><topic>Microtubules - physiology</topic><topic>Mitosis</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Ovarian Neoplasms</topic><topic>Paclitaxel - toxicity</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><topic>Phosphorylation</topic><topic>Proteasome Endopeptidase Complex</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Santé publique et épidémiologie</topic><topic>Subcellular Processes</topic><topic>Tumor Cells, Cultured</topic><topic>Virulence Factors, Bordetella - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chadebech, Philippe</creatorcontrib><creatorcontrib>Brichese, Laetitia</creatorcontrib><creatorcontrib>Baldin, Véronique</creatorcontrib><creatorcontrib>Vidal, Simone</creatorcontrib><creatorcontrib>Valette, Annie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chadebech, Philippe</au><au>Brichese, Laetitia</au><au>Baldin, Véronique</au><au>Vidal, Simone</au><au>Valette, Annie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorylation and Proteasome-Dependent Degradation of Bcl-2 in Mitotic-Arrested Cells after Microtubule Damage</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1999-09-07</date><risdate>1999</risdate><volume>262</volume><issue>3</issue><spage>823</spage><epage>827</epage><pages>823-827</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Treatment of NIH-OVCAR-3 cells with paclitaxel, a microtubule-stabilizing agent, induces mitotic arrest and apoptosis, but also Bcl-2 phosphorylation. We report here that Bcl-2 phosphorylation precedes Bcl-2 down-regulation and that both events are closely associated with mitotic arrest, but are not sufficient for paclitaxel to trigger apoptosis. Indeed, when paclitaxel-treated cells were induced to exit mitosis in the presence of 2-aminopurine, Bcl-2 phosphorylation and Bcl-2 down-regulation were both inhibited. In contrast, when apoptosis was inhibited by a caspase inhibitor or Bcl-2 over-expression, Bcl-2 phosphorylation and down-regulation still occurred. Furthermore, we show that Bcl-2 is degraded in mitosis by the proteasome-dependent pathway since Bcl-2 down-regulation is inhibited by proteasome inhibitors such as MG132, Lactacystin and LLnL. Taken together these results indicate that mitotic spindle damage results in post-translational modifications of Bcl-2 by phosphorylation and degradation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10471409</pmid><doi>10.1006/bbrc.1999.1291</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-8523-0494</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 1999-09, Vol.262 (3), p.823-827 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Acetylcysteine - analogs & derivatives Acetylcysteine - pharmacology Amino Acid Chloromethyl Ketones - pharmacology Apoptosis Biochemistry Biochemistry, Molecular Biology Cell Behavior Cellular Biology Cysteine Endopeptidases - metabolism Cysteine Proteinase Inhibitors - pharmacology Female Gene Expression Regulation, Neoplastic Genes, bcl-2 Humans Leupeptins - pharmacology Life Sciences Microtubules - drug effects Microtubules - physiology Mitosis Multienzyme Complexes - metabolism Ovarian Neoplasms Paclitaxel - toxicity Pharmaceutical sciences Pharmacology Phosphorylation Proteasome Endopeptidase Complex Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Santé publique et épidémiologie Subcellular Processes Tumor Cells, Cultured Virulence Factors, Bordetella - pharmacology |
| title | Phosphorylation and Proteasome-Dependent Degradation of Bcl-2 in Mitotic-Arrested Cells after Microtubule Damage |
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