p53-dependent transcription can exhibit both on off and graded response after genotoxic stress
The p53 protein is a central player in cellular response to DNA damage. Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every si...
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| Veröffentlicht in: | Oncogene 2004-08, Vol.23 (37), p.6175-6185 |
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| creator | Jõers, Arvi Jaks, Viljar Kase, Johanna Maimets, Toivo |
| description | The p53 protein is a central player in cellular response to DNA damage. Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every single cell responds simultaneously and similarly to its neighbor) or heterogeneously (where only some cells of a population respond and the number of these increases with increasing dose of inducer). We have studied here the p53 response to DNA-damaging agents (camptothecin, mitomycin C) in individual cells. We show that the level of p53 protein is increased in every single cell of the population homogeneously, while the p53-dependent transcription can be subject to an on/off-type response. Depending on the structure of the target promoter, p53-dependent transcription can be regulated according to the binary or graded model. The on/off-type transcriptional activation pattern of p53 defines two distinct subpopulations of cells after DNA damage. |
| doi_str_mv | 10.1038/sj.onc.1207864 |
| format | Article |
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Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every single cell responds simultaneously and similarly to its neighbor) or heterogeneously (where only some cells of a population respond and the number of these increases with increasing dose of inducer). We have studied here the p53 response to DNA-damaging agents (camptothecin, mitomycin C) in individual cells. We show that the level of p53 protein is increased in every single cell of the population homogeneously, while the p53-dependent transcription can be subject to an on/off-type response. Depending on the structure of the target promoter, p53-dependent transcription can be regulated according to the binary or graded model. The on/off-type transcriptional activation pattern of p53 defines two distinct subpopulations of cells after DNA damage.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1207864</identifier><identifier>PMID: 15208667</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Apoptosis ; Base Sequence ; Biological and medical sciences ; Blotting, Western ; Camptothecin ; Cell Biology ; Cell cycle ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Deoxyribonucleic acid ; DNA ; DNA Damage ; DNA Primers ; Fluorescent Antibody Technique ; Fundamental and applied biological sciences. Psychology ; Genetic engineering ; Genotoxicity ; Green Fluorescent Proteins ; Human Genetics ; Internal Medicine ; Luminescent Proteins - genetics ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Mitomycin C ; Molecular and cellular biology ; Molecular genetics ; Mutagens - toxicity ; Oncology ; original-paper ; p53 Protein ; Proteins ; Transcription activation ; Transcription factors ; Transcription, Genetic - physiology ; Transcription. Transcription factor. Splicing. Rna processing ; Tumor Suppressor Protein p53 - physiology ; Tumors</subject><ispartof>Oncogene, 2004-08, Vol.23 (37), p.6175-6185</ispartof><rights>Springer Nature Limited 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 19, 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c636t-53ece4510619299fad9419dfa81eebab132ddb306a52b17b4ed0e4a83d043db43</citedby><cites>FETCH-LOGICAL-c636t-53ece4510619299fad9419dfa81eebab132ddb306a52b17b4ed0e4a83d043db43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1207864$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1207864$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16036755$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15208667$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:110426211$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Jõers, Arvi</creatorcontrib><creatorcontrib>Jaks, Viljar</creatorcontrib><creatorcontrib>Kase, Johanna</creatorcontrib><creatorcontrib>Maimets, Toivo</creatorcontrib><title>p53-dependent transcription can exhibit both on off and graded response after genotoxic stress</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>The p53 protein is a central player in cellular response to DNA damage. Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every single cell responds simultaneously and similarly to its neighbor) or heterogeneously (where only some cells of a population respond and the number of these increases with increasing dose of inducer). We have studied here the p53 response to DNA-damaging agents (camptothecin, mitomycin C) in individual cells. We show that the level of p53 protein is increased in every single cell of the population homogeneously, while the p53-dependent transcription can be subject to an on/off-type response. Depending on the structure of the target promoter, p53-dependent transcription can be regulated according to the binary or graded model. The on/off-type transcriptional activation pattern of p53 defines two distinct subpopulations of cells after DNA damage.</description><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Camptothecin</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA Primers</subject><subject>Fluorescent Antibody Technique</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic engineering</subject><subject>Genotoxicity</subject><subject>Green Fluorescent Proteins</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Luminescent Proteins - genetics</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mitomycin C</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Mutagens - toxicity</subject><subject>Oncology</subject><subject>original-paper</subject><subject>p53 Protein</subject><subject>Proteins</subject><subject>Transcription activation</subject><subject>Transcription factors</subject><subject>Transcription, Genetic - physiology</subject><subject>Transcription. Transcription factor. Splicing. Rna processing</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</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>eNp1kk1v1DAQhiMEoqVw5QayQHDL1t-Jj1XFl1SJC1yxHHuy9bJrB9tRy7_H1QYiIa18sDXzvDMe-22alwRvCGb9Zd5tYrAbQnHXS_6oOSe8k60Qij9uzrESuFWU0bPmWc47jHGnMH3anBFBcS9ld978mARrHUwQHISCSjIh2-Sn4mNA1gQE97d-8AUNsdyiGovjiExwaJuMA4cS5CmGDMiMBRLaQogl3nuLcqmp_Lx5Mpp9hhfLftF8__jh2_Xn9ubrpy_XVzetlUyWVjCwwAXBkiiq1Gic4kS50fQEYDADYdS5gWFpBB1IN3BwGLjpmcOcuYGzi6Y91s13MM2DnpI_mPRbR-P1EvpZT6BFLzB_4NVJfkrRraK_QkIwp5ISUrXvj9oK_pohF33w2cJ-bwLEOWvSY97VNhV8-x-4i3MK9R00lZww1rG-q9SbkxTtmFSS0wptjtDW7EH7MMb6U7YuBwdvY4DR1_gV6RVhnHG5CmyKOScY_41IsH5wjs47XZ2jF-dUwevlGvNwALfii1Uq8G4BTLZmP1anWJ9XTmImOyEqd7k8bU2FLaR1npOtXx0VwZQ5wVpyyf8B0qvmkQ</recordid><startdate>20040819</startdate><enddate>20040819</enddate><creator>Jõers, Arvi</creator><creator>Jaks, Viljar</creator><creator>Kase, Johanna</creator><creator>Maimets, Toivo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><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>3V.</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>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>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20040819</creationdate><title>p53-dependent transcription can exhibit both on off and graded response after genotoxic stress</title><author>Jõers, Arvi ; Jaks, Viljar ; Kase, Johanna ; Maimets, Toivo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c636t-53ece4510619299fad9419dfa81eebab132ddb306a52b17b4ed0e4a83d043db43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Camptothecin</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>DNA Primers</topic><topic>Fluorescent Antibody Technique</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic engineering</topic><topic>Genotoxicity</topic><topic>Green Fluorescent Proteins</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Luminescent Proteins - genetics</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mitomycin C</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Mutagens - toxicity</topic><topic>Oncology</topic><topic>original-paper</topic><topic>p53 Protein</topic><topic>Proteins</topic><topic>Transcription activation</topic><topic>Transcription factors</topic><topic>Transcription, Genetic - physiology</topic><topic>Transcription. Transcription factor. Splicing. Rna processing</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jõers, Arvi</creatorcontrib><creatorcontrib>Jaks, Viljar</creatorcontrib><creatorcontrib>Kase, Johanna</creatorcontrib><creatorcontrib>Maimets, Toivo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jõers, Arvi</au><au>Jaks, Viljar</au><au>Kase, Johanna</au><au>Maimets, Toivo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53-dependent transcription can exhibit both on off and graded response after genotoxic stress</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2004-08-19</date><risdate>2004</risdate><volume>23</volume><issue>37</issue><spage>6175</spage><epage>6185</epage><pages>6175-6185</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>The p53 protein is a central player in cellular response to DNA damage. Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every single cell responds simultaneously and similarly to its neighbor) or heterogeneously (where only some cells of a population respond and the number of these increases with increasing dose of inducer). We have studied here the p53 response to DNA-damaging agents (camptothecin, mitomycin C) in individual cells. We show that the level of p53 protein is increased in every single cell of the population homogeneously, while the p53-dependent transcription can be subject to an on/off-type response. Depending on the structure of the target promoter, p53-dependent transcription can be regulated according to the binary or graded model. The on/off-type transcriptional activation pattern of p53 defines two distinct subpopulations of cells after DNA damage.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15208667</pmid><doi>10.1038/sj.onc.1207864</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Base Sequence Biological and medical sciences Blotting, Western Camptothecin Cell Biology Cell cycle Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Deoxyribonucleic acid DNA DNA Damage DNA Primers Fluorescent Antibody Technique Fundamental and applied biological sciences. Psychology Genetic engineering Genotoxicity Green Fluorescent Proteins Human Genetics Internal Medicine Luminescent Proteins - genetics Medicin och hälsovetenskap Medicine Medicine & Public Health Mitomycin C Molecular and cellular biology Molecular genetics Mutagens - toxicity Oncology original-paper p53 Protein Proteins Transcription activation Transcription factors Transcription, Genetic - physiology Transcription. Transcription factor. Splicing. Rna processing Tumor Suppressor Protein p53 - physiology Tumors |
| title | p53-dependent transcription can exhibit both on off and graded response after genotoxic stress |
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