Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation
Eukaryotic cells activate an evolutionarily conserved set of proteins that rapidly induce cell cycle arrest to prevent replication or segregation of damaged DNA before repair is completed. In response to ionizing radiation (IR), the cell cycle checkpoint kinase, Chk2 (hCds1), is phosphorylated and a...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2000-11, Vol.60 (21), p.5934-5936 |
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| container_issue | 21 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | AHN, Joon-Young SCHWARZ, Julie K PIWNICA-WORMS, Helen CANMAN, Christine E |
| description | Eukaryotic cells activate an evolutionarily conserved set of proteins that rapidly induce cell cycle arrest to prevent replication or segregation of damaged DNA before repair is completed. In response to ionizing radiation (IR), the cell cycle checkpoint kinase, Chk2 (hCds1), is phosphorylated and activated in an ataxia telangiectasia mutated (ATM)-dependent manner. Here we show that the ATM protein kinase directly phosphorylates T68 within the SQ/TQ-rich domain of Chk2 in vitro and that T68 is phosphorylated in vivo in response to IR in an ATM-dependent manner. Furthermore, phosphorylation of T68 was required for full activation of Chk2 after IR. Together, these data are consistent with the model that ATM directly phosphorylates Chk2 in vivo and that this event contributes to the activation of Chk2 in irradiated cells. |
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In response to ionizing radiation (IR), the cell cycle checkpoint kinase, Chk2 (hCds1), is phosphorylated and activated in an ataxia telangiectasia mutated (ATM)-dependent manner. Here we show that the ATM protein kinase directly phosphorylates T68 within the SQ/TQ-rich domain of Chk2 in vitro and that T68 is phosphorylated in vivo in response to IR in an ATM-dependent manner. Furthermore, phosphorylation of T68 was required for full activation of Chk2 after IR. Together, these data are consistent with the model that ATM directly phosphorylates Chk2 in vivo and that this event contributes to the activation of Chk2 in irradiated cells.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11085506</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Amino Acid Sequence ; Animals ; Ataxia Telangiectasia Mutated Proteins ; Biological and medical sciences ; Biological effects of radiation ; Cell Cycle - physiology ; Cell Cycle Proteins ; Cell cycle, cell proliferation ; Cell physiology ; Checkpoint Kinase 2 ; DNA-Binding Proteins ; Enzyme Activation - radiation effects ; Fibroblasts - enzymology ; Fibroblasts - radiation effects ; Fundamental and applied biological sciences. Psychology ; Humans ; Ionizing radiations ; Mice ; Molecular and cellular biology ; Molecular Sequence Data ; Neuroblastoma ; Phosphorylation - radiation effects ; Protein Kinases - metabolism ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases - metabolism ; Threonine - metabolism ; Tissues, organs and organisms biophysics ; Transfection ; Tumor Cells, Cultured - enzymology ; Tumor Cells, Cultured - radiation effects ; Tumor Suppressor Proteins</subject><ispartof>Cancer research (Chicago, Ill.), 2000-11, Vol.60 (21), p.5934-5936</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=798190$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11085506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AHN, Joon-Young</creatorcontrib><creatorcontrib>SCHWARZ, Julie K</creatorcontrib><creatorcontrib>PIWNICA-WORMS, Helen</creatorcontrib><creatorcontrib>CANMAN, Christine E</creatorcontrib><title>Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Eukaryotic cells activate an evolutionarily conserved set of proteins that rapidly induce cell cycle arrest to prevent replication or segregation of damaged DNA before repair is completed. In response to ionizing radiation (IR), the cell cycle checkpoint kinase, Chk2 (hCds1), is phosphorylated and activated in an ataxia telangiectasia mutated (ATM)-dependent manner. Here we show that the ATM protein kinase directly phosphorylates T68 within the SQ/TQ-rich domain of Chk2 in vitro and that T68 is phosphorylated in vivo in response to IR in an ATM-dependent manner. Furthermore, phosphorylation of T68 was required for full activation of Chk2 after IR. Together, these data are consistent with the model that ATM directly phosphorylates Chk2 in vivo and that this event contributes to the activation of Chk2 in irradiated cells.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Ataxia Telangiectasia Mutated Proteins</subject><subject>Biological and medical sciences</subject><subject>Biological effects of radiation</subject><subject>Cell Cycle - physiology</subject><subject>Cell Cycle Proteins</subject><subject>Cell cycle, cell proliferation</subject><subject>Cell physiology</subject><subject>Checkpoint Kinase 2</subject><subject>DNA-Binding Proteins</subject><subject>Enzyme Activation - radiation effects</subject><subject>Fibroblasts - enzymology</subject><subject>Fibroblasts - radiation effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Ionizing radiations</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Neuroblastoma</subject><subject>Phosphorylation - radiation effects</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Structure, Tertiary</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Threonine - metabolism</subject><subject>Tissues, organs and organisms biophysics</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured - enzymology</subject><subject>Tumor Cells, Cultured - radiation effects</subject><subject>Tumor Suppressor Proteins</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtLAzEUhYMotlb_ggRcD-Q1M5mlFF9QcFPXJY-bTnSaqUkq1t_gjzbY6uJwz-F8nMU9QVNac1m1QtSnaEoIkVUtWjZBFym9llhTUp-jCaVE1jVppuh72UcYgw-AG4m3_ZiK4n5Q2Y8B6z1WWX16hTMMKqw9mKxSiZtdVhks9glHeN_5WLwbIwbnvPEQMlYm-4_DyujwvH9j2IcCp-0YEuA84lL5Lx_WOCrrf8lLdObUkODqeGfo5f5uOX-sFs8PT_PbRdUzLnPVCAsda5nRjjGrZasF14rrljoJnRUUDCFaOeqsaCxwxgG6pjSgBTFdx2fo-rC73ekN2NU2-o2K-9XfWwpwcwRUMmpwUQXj0z_XdpJ2hP8Asj9wSA</recordid><startdate>20001101</startdate><enddate>20001101</enddate><creator>AHN, Joon-Young</creator><creator>SCHWARZ, Julie K</creator><creator>PIWNICA-WORMS, Helen</creator><creator>CANMAN, Christine E</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20001101</creationdate><title>Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation</title><author>AHN, Joon-Young ; SCHWARZ, Julie K ; PIWNICA-WORMS, Helen ; CANMAN, Christine E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h238t-64de9272cbf22db87b43ba3b71f8e9d41ec00baf1fd46de323ee96e9deb40c993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Ataxia Telangiectasia Mutated Proteins</topic><topic>Biological and medical sciences</topic><topic>Biological effects of radiation</topic><topic>Cell Cycle - physiology</topic><topic>Cell Cycle Proteins</topic><topic>Cell cycle, cell proliferation</topic><topic>Cell physiology</topic><topic>Checkpoint Kinase 2</topic><topic>DNA-Binding Proteins</topic><topic>Enzyme Activation - radiation effects</topic><topic>Fibroblasts - enzymology</topic><topic>Fibroblasts - radiation effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Ionizing radiations</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Neuroblastoma</topic><topic>Phosphorylation - radiation effects</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Structure, Tertiary</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Threonine - metabolism</topic><topic>Tissues, organs and organisms biophysics</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured - enzymology</topic><topic>Tumor Cells, Cultured - radiation effects</topic><topic>Tumor Suppressor Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AHN, Joon-Young</creatorcontrib><creatorcontrib>SCHWARZ, Julie K</creatorcontrib><creatorcontrib>PIWNICA-WORMS, Helen</creatorcontrib><creatorcontrib>CANMAN, Christine E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>AHN, Joon-Young</au><au>SCHWARZ, Julie K</au><au>PIWNICA-WORMS, Helen</au><au>CANMAN, Christine E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2000-11-01</date><risdate>2000</risdate><volume>60</volume><issue>21</issue><spage>5934</spage><epage>5936</epage><pages>5934-5936</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Eukaryotic cells activate an evolutionarily conserved set of proteins that rapidly induce cell cycle arrest to prevent replication or segregation of damaged DNA before repair is completed. In response to ionizing radiation (IR), the cell cycle checkpoint kinase, Chk2 (hCds1), is phosphorylated and activated in an ataxia telangiectasia mutated (ATM)-dependent manner. Here we show that the ATM protein kinase directly phosphorylates T68 within the SQ/TQ-rich domain of Chk2 in vitro and that T68 is phosphorylated in vivo in response to IR in an ATM-dependent manner. Furthermore, phosphorylation of T68 was required for full activation of Chk2 after IR. Together, these data are consistent with the model that ATM directly phosphorylates Chk2 in vivo and that this event contributes to the activation of Chk2 in irradiated cells.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11085506</pmid><tpages>3</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2000-11, Vol.60 (21), p.5934-5936 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Sequence Animals Ataxia Telangiectasia Mutated Proteins Biological and medical sciences Biological effects of radiation Cell Cycle - physiology Cell Cycle Proteins Cell cycle, cell proliferation Cell physiology Checkpoint Kinase 2 DNA-Binding Proteins Enzyme Activation - radiation effects Fibroblasts - enzymology Fibroblasts - radiation effects Fundamental and applied biological sciences. Psychology Humans Ionizing radiations Mice Molecular and cellular biology Molecular Sequence Data Neuroblastoma Phosphorylation - radiation effects Protein Kinases - metabolism Protein Structure, Tertiary Protein-Serine-Threonine Kinases - metabolism Threonine - metabolism Tissues, organs and organisms biophysics Transfection Tumor Cells, Cultured - enzymology Tumor Cells, Cultured - radiation effects Tumor Suppressor Proteins |
| title | Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation |
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