Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2
The apoptotic initiator caspase‐2 has been implicated in oocyte death, in DNA damage‐ and heat shock‐induced death, and in mitotic catastrophe. We show here that the mitosis‐promoting kinase, cdk1–cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome c release by phosphorylating caspa...
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| Veröffentlicht in: | The EMBO journal 2009-10, Vol.28 (20), p.3216-3227 |
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| creator | Andersen, Joshua L Johnson, Carrie E Freel, Christopher D Parrish, Amanda B Day, Jennifer L Buchakjian, Marisa R Nutt, Leta K Thompson, J Will Moseley, M Arthur Kornbluth, Sally |
| description | The apoptotic initiator caspase‐2 has been implicated in oocyte death, in DNA damage‐ and heat shock‐induced death, and in mitotic catastrophe. We show here that the mitosis‐promoting kinase, cdk1–cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome
c
release by phosphorylating caspase‐2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase‐2 interdomain, prevents caspase‐2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase‐2 detected during interphase was lost in mitosis. Expression of S340A non‐phosphorylatable caspase‐2 abrogated mitotic suppression of caspase‐2 and apoptosis in various settings, including oocytes induced to undergo cdk1‐dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase‐2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase‐2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase‐2 and suggest that under conditions of mitotic arrest, cdk1–cyclin B1 activity must be overcome for apoptosis to occur. |
| doi_str_mv | 10.1038/emboj.2009.253 |
| format | Article |
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release by phosphorylating caspase‐2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase‐2 interdomain, prevents caspase‐2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase‐2 detected during interphase was lost in mitosis. Expression of S340A non‐phosphorylatable caspase‐2 abrogated mitotic suppression of caspase‐2 and apoptosis in various settings, including oocytes induced to undergo cdk1‐dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase‐2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase‐2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase‐2 and suggest that under conditions of mitotic arrest, cdk1–cyclin B1 activity must be overcome for apoptosis to occur.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2009.253</identifier><identifier>PMID: 19730412</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Apoptosis ; Apoptosis - genetics ; Apoptosis - physiology ; Caspase 2 - genetics ; Caspase 2 - metabolism ; caspase-2 ; CDC2 Protein Kinase - genetics ; CDC2 Protein Kinase - metabolism ; cdk1 ; Cell division ; Cell Line ; Cell Line, Tumor ; Cyclin B - genetics ; Cyclin B - metabolism ; Cyclin B1 ; Cytochrome ; Deoxyribonucleic acid ; DNA ; Electrophoresis, Polyacrylamide Gel ; EMBO06 ; EMBO07 ; Evolutionary biology ; Genetic Vectors ; Humans ; Kinases ; Lentivirus ; mitosis ; Mitosis - drug effects ; Mitosis - genetics ; Mitosis - physiology ; Molecular biology ; Mortality ; Nocodazole - pharmacology ; Oocytes ; Phosphorylation ; RNA, Small Interfering ; Serine - genetics ; Serine - metabolism ; Serine - physiology ; Xenopus</subject><ispartof>The EMBO journal, 2009-10, Vol.28 (20), p.3216-3227</ispartof><rights>European Molecular Biology Organization 2009</rights><rights>Copyright © 2009 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Oct 21, 2009</rights><rights>Copyright © 2009, European Molecular Biology Organization 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5413-728270384bf8bbe31bf8b14dbb19f1883e086f6132d32ced7175e428ba8efe493</citedby><cites>FETCH-LOGICAL-c5413-728270384bf8bbe31bf8b14dbb19f1883e086f6132d32ced7175e428ba8efe493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771089/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771089/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2009.253$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19730412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andersen, Joshua L</creatorcontrib><creatorcontrib>Johnson, Carrie E</creatorcontrib><creatorcontrib>Freel, Christopher D</creatorcontrib><creatorcontrib>Parrish, Amanda B</creatorcontrib><creatorcontrib>Day, Jennifer L</creatorcontrib><creatorcontrib>Buchakjian, Marisa R</creatorcontrib><creatorcontrib>Nutt, Leta K</creatorcontrib><creatorcontrib>Thompson, J Will</creatorcontrib><creatorcontrib>Moseley, M Arthur</creatorcontrib><creatorcontrib>Kornbluth, Sally</creatorcontrib><title>Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>The apoptotic initiator caspase‐2 has been implicated in oocyte death, in DNA damage‐ and heat shock‐induced death, and in mitotic catastrophe. We show here that the mitosis‐promoting kinase, cdk1–cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome
c
release by phosphorylating caspase‐2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase‐2 interdomain, prevents caspase‐2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase‐2 detected during interphase was lost in mitosis. Expression of S340A non‐phosphorylatable caspase‐2 abrogated mitotic suppression of caspase‐2 and apoptosis in various settings, including oocytes induced to undergo cdk1‐dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase‐2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase‐2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase‐2 and suggest that under conditions of mitotic arrest, cdk1–cyclin B1 activity must be overcome for apoptosis to occur.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - physiology</subject><subject>Caspase 2 - genetics</subject><subject>Caspase 2 - metabolism</subject><subject>caspase-2</subject><subject>CDC2 Protein Kinase - genetics</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>cdk1</subject><subject>Cell division</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cyclin B - genetics</subject><subject>Cyclin B - metabolism</subject><subject>Cyclin B1</subject><subject>Cytochrome</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Electrophoresis, Polyacrylamide 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We show here that the mitosis‐promoting kinase, cdk1–cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome
c
release by phosphorylating caspase‐2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase‐2 interdomain, prevents caspase‐2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase‐2 detected during interphase was lost in mitosis. Expression of S340A non‐phosphorylatable caspase‐2 abrogated mitotic suppression of caspase‐2 and apoptosis in various settings, including oocytes induced to undergo cdk1‐dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase‐2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase‐2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase‐2 and suggest that under conditions of mitotic arrest, cdk1–cyclin B1 activity must be overcome for apoptosis to occur.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>19730412</pmid><doi>10.1038/emboj.2009.253</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Apoptosis - genetics Apoptosis - physiology Caspase 2 - genetics Caspase 2 - metabolism caspase-2 CDC2 Protein Kinase - genetics CDC2 Protein Kinase - metabolism cdk1 Cell division Cell Line Cell Line, Tumor Cyclin B - genetics Cyclin B - metabolism Cyclin B1 Cytochrome Deoxyribonucleic acid DNA Electrophoresis, Polyacrylamide Gel EMBO06 EMBO07 Evolutionary biology Genetic Vectors Humans Kinases Lentivirus mitosis Mitosis - drug effects Mitosis - genetics Mitosis - physiology Molecular biology Mortality Nocodazole - pharmacology Oocytes Phosphorylation RNA, Small Interfering Serine - genetics Serine - metabolism Serine - physiology Xenopus |
| title | Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2 |
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