Proteome Half-Life Dynamics in Living Human Cells
Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicabl...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2011-02, Vol.331 (6018), p.764-768 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Eden, Eran Geva-Zatorsky, Naama Issaeva, Irina Cohen, Ariel Dekel, Erez Danon, Tamar Cohen, Lydia Mayo, Avi Alon, Uri |
| description | Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells. |
| doi_str_mv | 10.1126/science.1199784 |
| format | Article |
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The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1199784</identifier><identifier>PMID: 21233346</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Anaphase-Promoting Complex-Cyclosome ; Antineoplastic Agents - pharmacology ; Antineoplastics ; Biological and medical sciences ; Bleaching ; Camptothecin - pharmacology ; Cancer ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell Death ; Cell division ; Cell Division - drug effects ; Cell growth ; Cell Line, Tumor ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cells ; Cytoplasm - metabolism ; Degradation ; Diverse techniques ; Dynamics ; Fluorescence ; Fundamental and applied biological sciences. Psychology ; Half lives ; Half-Life ; Human ; Humans ; Killing ; Light ; Luminescent Proteins ; Microscopy, Fluorescence ; Molecular and cellular biology ; Plugs ; Proteins ; Proteins - metabolism ; Proteome - metabolism ; Proteomes ; Radioactive decay ; rev genes ; Stress, Physiological ; Ubiquitin-Protein Ligase Complexes - metabolism</subject><ispartof>Science (American Association for the Advancement of Science), 2011-02, Vol.331 (6018), p.764-768</ispartof><rights>Copyright © 2011 American Association for the Advancement of Science</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-aa7a8c777a6df13b232bcb6de1c73876a6769ff7412370c042edefbd30c8428b3</citedby><cites>FETCH-LOGICAL-c470t-aa7a8c777a6df13b232bcb6de1c73876a6769ff7412370c042edefbd30c8428b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25790298$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25790298$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23854044$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21233346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eden, Eran</creatorcontrib><creatorcontrib>Geva-Zatorsky, Naama</creatorcontrib><creatorcontrib>Issaeva, Irina</creatorcontrib><creatorcontrib>Cohen, Ariel</creatorcontrib><creatorcontrib>Dekel, Erez</creatorcontrib><creatorcontrib>Danon, Tamar</creatorcontrib><creatorcontrib>Cohen, Lydia</creatorcontrib><creatorcontrib>Mayo, Avi</creatorcontrib><creatorcontrib>Alon, Uri</creatorcontrib><title>Proteome Half-Life Dynamics in Living Human Cells</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. 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Action of oncogenes and antioncogenes</subject><subject>Cells</subject><subject>Cytoplasm - metabolism</subject><subject>Degradation</subject><subject>Diverse techniques</subject><subject>Dynamics</subject><subject>Fluorescence</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Half lives</subject><subject>Half-Life</subject><subject>Human</subject><subject>Humans</subject><subject>Killing</subject><subject>Light</subject><subject>Luminescent Proteins</subject><subject>Microscopy, Fluorescence</subject><subject>Molecular and cellular biology</subject><subject>Plugs</subject><subject>Proteins</subject><subject>Proteins - metabolism</subject><subject>Proteome - metabolism</subject><subject>Proteomes</subject><subject>Radioactive decay</subject><subject>rev genes</subject><subject>Stress, Physiological</subject><subject>Ubiquitin-Protein Ligase Complexes - metabolism</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1LwzAchoMobk7PntRexFPdLx9tkqPMjwkDBd25pGkyMtZ2Jp2w_96MVXf0FML75M3Lg9AlhnuMST4O2plGm3iRkgt2hIYYZJZKAvQYDQFongrg2QCdhbAEiJmkp2hAMKGUsnyI8LtvO9PWJpmqlU1nzprkcduo2umQuCaZuW_XLJLpplZNMjGrVThHJ1atgrnozxGaPz99Tqbp7O3ldfIwSzXj0KVKcSU051zllcW0JJSUuswrgzWngucq57m0lrM4hYMGRkxlbFlR0IIRUdIRutv3rn37tTGhK2oXdFygGtNuQiGBS8Ykz_4lRYYZlxA_GqHxntS-DcEbW6y9q5XfFhiKndCiF1r0QuOL6757U9am-uN_DUbgtgdU0FGhV4124cBRkTFgu6KrPbcMXesPeRaXESlifrPPrWoLtfCxY_5BAFPAkgHllP4AydiQFA</recordid><startdate>20110211</startdate><enddate>20110211</enddate><creator>Eden, Eran</creator><creator>Geva-Zatorsky, Naama</creator><creator>Issaeva, Irina</creator><creator>Cohen, Ariel</creator><creator>Dekel, Erez</creator><creator>Danon, Tamar</creator><creator>Cohen, Lydia</creator><creator>Mayo, Avi</creator><creator>Alon, Uri</creator><general>American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</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>7X8</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20110211</creationdate><title>Proteome Half-Life Dynamics in Living Human Cells</title><author>Eden, Eran ; Geva-Zatorsky, Naama ; Issaeva, Irina ; Cohen, Ariel ; Dekel, Erez ; Danon, Tamar ; Cohen, Lydia ; Mayo, Avi ; Alon, Uri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-aa7a8c777a6df13b232bcb6de1c73876a6769ff7412370c042edefbd30c8428b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anaphase-Promoting Complex-Cyclosome</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastics</topic><topic>Biological and medical sciences</topic><topic>Bleaching</topic><topic>Camptothecin - pharmacology</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Death</topic><topic>Cell division</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cells</topic><topic>Cytoplasm - metabolism</topic><topic>Degradation</topic><topic>Diverse techniques</topic><topic>Dynamics</topic><topic>Fluorescence</topic><topic>Fundamental and applied biological sciences. 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| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2011-02, Vol.331 (6018), p.764-768 |
| issn | 0036-8075 1095-9203 |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Anaphase-Promoting Complex-Cyclosome Antineoplastic Agents - pharmacology Antineoplastics Biological and medical sciences Bleaching Camptothecin - pharmacology Cancer Cell cycle Cell Cycle Proteins - metabolism Cell Death Cell division Cell Division - drug effects Cell growth Cell Line, Tumor Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cells Cytoplasm - metabolism Degradation Diverse techniques Dynamics Fluorescence Fundamental and applied biological sciences. Psychology Half lives Half-Life Human Humans Killing Light Luminescent Proteins Microscopy, Fluorescence Molecular and cellular biology Plugs Proteins Proteins - metabolism Proteome - metabolism Proteomes Radioactive decay rev genes Stress, Physiological Ubiquitin-Protein Ligase Complexes - metabolism |
| title | Proteome Half-Life Dynamics in Living Human Cells |
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