The protein kinase PKR: a molecular clock that sequentially activates survival and death programs
Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The...
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| Veröffentlicht in: | The EMBO journal 2004-02, Vol.23 (3), p.564-571 |
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| creator | Donzé, Olivier Deng, Jing Curran, Joseph Sladek, Robert Picard, Didier Sonenberg, Nahum |
| description | Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon‐induced protein kinase PKR acts as a molecular clock by using catalysis‐dependent and ‐independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF‐κB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF‐2α. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions. |
| doi_str_mv | 10.1038/sj.emboj.7600078 |
| format | Article |
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The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon‐induced protein kinase PKR acts as a molecular clock by using catalysis‐dependent and ‐independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF‐κB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF‐2α. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/sj.emboj.7600078</identifier><identifier>PMID: 14749731</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; apoptosis ; Apoptosis - physiology ; Catalysis ; cell survival ; Cell Survival - physiology ; eIF-2 Kinase - metabolism ; eIF-2α kinase ; EMBO07 ; EMBO37 ; Eukaryotic Initiation Factor-2 - metabolism ; Immune system ; Mice ; Mortality ; NF-kappa B - metabolism ; NF-κB ; NIH 3T3 Cells ; Phosphorylation ; Signal Transduction - physiology ; Survival ; temporal activation</subject><ispartof>The EMBO journal, 2004-02, Vol.23 (3), p.564-571</ispartof><rights>European Molecular Biology Organization 2004</rights><rights>Copyright © 2004 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Feb 11, 2004</rights><rights>Copyright © 2004, European Molecular Biology Organization 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5718-d115c97d2204e75cb45d1ba4c2293875196d9a9fca8c4c43b392aee42301bad03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1271809/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1271809/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/sj.emboj.7600078$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14749731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Donzé, Olivier</creatorcontrib><creatorcontrib>Deng, Jing</creatorcontrib><creatorcontrib>Curran, Joseph</creatorcontrib><creatorcontrib>Sladek, Robert</creatorcontrib><creatorcontrib>Picard, Didier</creatorcontrib><creatorcontrib>Sonenberg, Nahum</creatorcontrib><title>The protein kinase PKR: a molecular clock that sequentially activates survival and death programs</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon‐induced protein kinase PKR acts as a molecular clock by using catalysis‐dependent and ‐independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF‐κB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF‐2α. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.</description><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Catalysis</subject><subject>cell survival</subject><subject>Cell Survival - physiology</subject><subject>eIF-2 Kinase - metabolism</subject><subject>eIF-2α kinase</subject><subject>EMBO07</subject><subject>EMBO37</subject><subject>Eukaryotic Initiation Factor-2 - metabolism</subject><subject>Immune system</subject><subject>Mice</subject><subject>Mortality</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB</subject><subject>NIH 3T3 Cells</subject><subject>Phosphorylation</subject><subject>Signal Transduction - physiology</subject><subject>Survival</subject><subject>temporal activation</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkcFv0zAUxiMEYt3gzgVkcdgtxXacOOYwCabRsY6B0NCO1ovz2qZ1kmInhf73eKRqBxLiZEvv933ve_qi6AWjY0aT_I1fjrEu2uVYZpRSmT-KRkxkNOZUpo-jEeUZiwXL1VF07P0yIGku2dPoiAkplEzYKILbBZK1azusGrKqGvBIvky_viVA6tai6S04YmxrVqRbQEc8fu-x6SqwdkvAdNUGOvTE924TvpZAU5ISoVvcm84d1P5Z9GQG1uPz3XsSfftwcXt-GV9_nnw8f3cdm1SyPC4ZS42SJedUoExNIdKSFSAM5yrJZcpUVipQMwO5EUYkRaI4IAqe0ICVNDmJzgbfdV_UWJqQ0oHVa1fV4La6hUr_OWmqhZ63G8142E9VMDjdGbg2HOk7XVfeoLXQYNt7nVMmhGA8gK__Apdt75pwnGYq5RmXlAWIDpBxrfcOZ_skjOr78rRf6t_l6V15QfLq4QUHwa6tAKgB-FFZ3P7XUF98en91MGeD1gdZM0f3IPS_A70cNA10vcP9wsM8HuaV7_DnfgxupTOZyFTf3Uz09PLmanKXT3WS_AKg1tPs</recordid><startdate>20040211</startdate><enddate>20040211</enddate><creator>Donzé, Olivier</creator><creator>Deng, Jing</creator><creator>Curran, Joseph</creator><creator>Sladek, Robert</creator><creator>Picard, Didier</creator><creator>Sonenberg, Nahum</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040211</creationdate><title>The protein kinase PKR: a molecular clock that sequentially activates survival and death programs</title><author>Donzé, Olivier ; Deng, Jing ; Curran, Joseph ; Sladek, Robert ; Picard, Didier ; Sonenberg, Nahum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5718-d115c97d2204e75cb45d1ba4c2293875196d9a9fca8c4c43b392aee42301bad03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>apoptosis</topic><topic>Apoptosis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Donzé, Olivier</au><au>Deng, Jing</au><au>Curran, Joseph</au><au>Sladek, Robert</au><au>Picard, Didier</au><au>Sonenberg, Nahum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The protein kinase PKR: a molecular clock that sequentially activates survival and death programs</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2004-02-11</date><risdate>2004</risdate><volume>23</volume><issue>3</issue><spage>564</spage><epage>571</epage><pages>564-571</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon‐induced protein kinase PKR acts as a molecular clock by using catalysis‐dependent and ‐independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF‐κB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF‐2α. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>14749731</pmid><doi>10.1038/sj.emboj.7600078</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals apoptosis Apoptosis - physiology Catalysis cell survival Cell Survival - physiology eIF-2 Kinase - metabolism eIF-2α kinase EMBO07 EMBO37 Eukaryotic Initiation Factor-2 - metabolism Immune system Mice Mortality NF-kappa B - metabolism NF-κB NIH 3T3 Cells Phosphorylation Signal Transduction - physiology Survival temporal activation |
| title | The protein kinase PKR: a molecular clock that sequentially activates survival and death programs |
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