The thyroid hormone receptor antagonizes CREB-mediated transcription
Combinatorial regulation of transcription involves binding of transcription factors to DNA as well as protein–protein interactions between them. In this paper, we demonstrate the existence of a mutual transcriptional antagonism between the thyroid hormone receptor (TR) and the cyclic AMP response el...
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| Veröffentlicht in: | The EMBO journal 2003-06, Vol.22 (12), p.3102-3112 |
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| description | Combinatorial regulation of transcription involves binding of transcription factors to DNA as well as protein–protein interactions between them. In this paper, we demonstrate the existence of a mutual transcriptional antagonism between the thyroid hormone receptor (TR) and the cyclic AMP response element binding protein (CREB), which involves a direct association of both transcription factors. TR inhibits transcriptional activity of CREB and represses activation of cAMP response element (CRE)‐containing promoters. TR does not bind to the CRE
in vitro
, but
in vivo
the liganded receptor is tethered to the promoter through protein–protein interactions. In turn, expression of CREB reduces TR‐dependent transcriptional responses. The association of TR with CREB inhibits the ability of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in the ligand‐dependent recruitment of the p160 coactivators by TR. These results indicate the existence of a transcriptional cross‐talk between CREB and TR signalling pathways, which can have important functional consequences. |
| doi_str_mv | 10.1093/emboj/cdg295 |
| format | Article |
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in vitro
, but
in vivo
the liganded receptor is tethered to the promoter through protein–protein interactions. In turn, expression of CREB reduces TR‐dependent transcriptional responses. The association of TR with CREB inhibits the ability of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in the ligand‐dependent recruitment of the p160 coactivators by TR. These results indicate the existence of a transcriptional cross‐talk between CREB and TR signalling pathways, which can have important functional consequences.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/cdg295</identifier><identifier>PMID: 12805224</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Cell Line ; CREB ; CREB phosphorylation ; CREB-Binding Protein ; Cyclic AMP Response Element-Binding Protein - genetics ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; EMBO09 ; EMBO37 ; Genes, Reporter ; Humans ; Hydroxamic Acids - metabolism ; Nuclear Proteins - metabolism ; Phosphorylation ; Pituitary Gland - cytology ; Pituitary Gland - metabolism ; Promoter Regions, Genetic ; Protein Synthesis Inhibitors - metabolism ; Receptors, Thyroid Hormone - genetics ; Receptors, Thyroid Hormone - metabolism ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Response Elements ; Signal Transduction - physiology ; Thyroid ; thyroid hormone receptor ; Trans-Activators - metabolism ; Transcription, Genetic ; transcriptional repression ; Triiodothyronine - metabolism</subject><ispartof>The EMBO journal, 2003-06, Vol.22 (12), p.3102-3112</ispartof><rights>European Molecular Biology Organization 2003</rights><rights>Copyright © 2003 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Jun 16, 2003</rights><rights>Copyright © 2003 European Molecular Biology Organization 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6696-be766176d31f8c79b21dde97a53a82cc3e61687dd1a141166cc32fce9d505b3c3</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/PMC162147/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC162147/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,1432,27922,27923,45572,45573,46407,46831,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12805224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aranda, Ana</creatorcontrib><creatorcontrib>Méndez-Pertuz, Marinela</creatorcontrib><creatorcontrib>Sánchez-Pacheco, Aurora</creatorcontrib><title>The thyroid hormone receptor antagonizes CREB-mediated transcription</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Combinatorial regulation of transcription involves binding of transcription factors to DNA as well as protein–protein interactions between them. In this paper, we demonstrate the existence of a mutual transcriptional antagonism between the thyroid hormone receptor (TR) and the cyclic AMP response element binding protein (CREB), which involves a direct association of both transcription factors. TR inhibits transcriptional activity of CREB and represses activation of cAMP response element (CRE)‐containing promoters. TR does not bind to the CRE
in vitro
, but
in vivo
the liganded receptor is tethered to the promoter through protein–protein interactions. In turn, expression of CREB reduces TR‐dependent transcriptional responses. The association of TR with CREB inhibits the ability of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in the ligand‐dependent recruitment of the p160 coactivators by TR. These results indicate the existence of a transcriptional cross‐talk between CREB and TR signalling pathways, which can have important functional consequences.</description><subject>Animals</subject><subject>Cell Line</subject><subject>CREB</subject><subject>CREB phosphorylation</subject><subject>CREB-Binding Protein</subject><subject>Cyclic AMP Response Element-Binding Protein - genetics</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>EMBO09</subject><subject>EMBO37</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Hydroxamic Acids - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Phosphorylation</subject><subject>Pituitary Gland - cytology</subject><subject>Pituitary Gland - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Synthesis Inhibitors - metabolism</subject><subject>Receptors, Thyroid Hormone - genetics</subject><subject>Receptors, Thyroid Hormone - metabolism</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Response Elements</subject><subject>Signal Transduction - physiology</subject><subject>Thyroid</subject><subject>thyroid hormone receptor</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription, Genetic</subject><subject>transcriptional repression</subject><subject>Triiodothyronine - metabolism</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</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>eNqFkUtv1DAUhSMEokNhxxYUsWBFqK8T28miCzoM5dHyUlERG8tj35nxkNiDnQDDrydtRtMB8VhZ8v3Oucc-SXIXyGMgVX6AzdQvD7SZ04pdS0ZQcJJRItj1ZEQoh6yAstpLbsW4JISwUsDNZA9oSRilxSh5erbAtF2sg7cmXfjQeIdpQI2r1odUuVbNvbM_MKbj95OjrEFjVYsmbYNyUQe7aq13t5MbM1VHvLM595MPzyZn4-fZyZvjF-MnJ5nmvOLZFAXnILjJYVZqUU0pGIOVUCxXJdU6Rw68FMaAggKA8_6KzjRWhhE2zXW-nxwOvqtu2ifR6PoYtVwF26iwll5Z-evE2YWc-68SOIVC9PqHG33wXzqMrWxs1FjXyqHvohR5LkpRwX9BKEtSMM578MFv4NJ3wfWfIKFilJXk0u3RAOngYww42yYGIi86lJcdyqHDHr-_-8oreFNaD7AB-GZrXP_TTE5Oj14K1kchF2GzQRd7iZtj2An75yD3Bt6ptgu4XXTl99c5Ebv7bGzx-3aswmfJRS6YPH99LM_fvmOfXsFHeZr_BBpy3ZI</recordid><startdate>20030616</startdate><enddate>20030616</enddate><creator>Aranda, Ana</creator><creator>Méndez-Pertuz, Marinela</creator><creator>Sánchez-Pacheco, Aurora</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>Oxford University Press</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>AEUYN</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>20030616</creationdate><title>The thyroid hormone receptor antagonizes CREB-mediated transcription</title><author>Aranda, Ana ; Méndez-Pertuz, Marinela ; Sánchez-Pacheco, Aurora</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6696-be766176d31f8c79b21dde97a53a82cc3e61687dd1a141166cc32fce9d505b3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Cell Line</topic><topic>CREB</topic><topic>CREB phosphorylation</topic><topic>CREB-Binding Protein</topic><topic>Cyclic AMP Response Element-Binding Protein - genetics</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>EMBO09</topic><topic>EMBO37</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Hydroxamic Acids - metabolism</topic><topic>Nuclear Proteins - metabolism</topic><topic>Phosphorylation</topic><topic>Pituitary Gland - cytology</topic><topic>Pituitary Gland - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Synthesis Inhibitors - metabolism</topic><topic>Receptors, Thyroid Hormone - genetics</topic><topic>Receptors, Thyroid Hormone - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Response Elements</topic><topic>Signal Transduction - physiology</topic><topic>Thyroid</topic><topic>thyroid hormone receptor</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription, Genetic</topic><topic>transcriptional repression</topic><topic>Triiodothyronine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aranda, Ana</creatorcontrib><creatorcontrib>Méndez-Pertuz, Marinela</creatorcontrib><creatorcontrib>Sánchez-Pacheco, Aurora</creatorcontrib><collection>Istex</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</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 One Sustainability</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>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</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 Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aranda, Ana</au><au>Méndez-Pertuz, Marinela</au><au>Sánchez-Pacheco, Aurora</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The thyroid hormone receptor antagonizes CREB-mediated transcription</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2003-06-16</date><risdate>2003</risdate><volume>22</volume><issue>12</issue><spage>3102</spage><epage>3112</epage><pages>3102-3112</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Combinatorial regulation of transcription involves binding of transcription factors to DNA as well as protein–protein interactions between them. In this paper, we demonstrate the existence of a mutual transcriptional antagonism between the thyroid hormone receptor (TR) and the cyclic AMP response element binding protein (CREB), which involves a direct association of both transcription factors. TR inhibits transcriptional activity of CREB and represses activation of cAMP response element (CRE)‐containing promoters. TR does not bind to the CRE
in vitro
, but
in vivo
the liganded receptor is tethered to the promoter through protein–protein interactions. In turn, expression of CREB reduces TR‐dependent transcriptional responses. The association of TR with CREB inhibits the ability of protein kinase A to phosphorylate CREB at Ser133, and leads to a reduction in the ligand‐dependent recruitment of the p160 coactivators by TR. These results indicate the existence of a transcriptional cross‐talk between CREB and TR signalling pathways, which can have important functional consequences.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>12805224</pmid><doi>10.1093/emboj/cdg295</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Cell Line CREB CREB phosphorylation CREB-Binding Protein Cyclic AMP Response Element-Binding Protein - genetics Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism EMBO09 EMBO37 Genes, Reporter Humans Hydroxamic Acids - metabolism Nuclear Proteins - metabolism Phosphorylation Pituitary Gland - cytology Pituitary Gland - metabolism Promoter Regions, Genetic Protein Synthesis Inhibitors - metabolism Receptors, Thyroid Hormone - genetics Receptors, Thyroid Hormone - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Response Elements Signal Transduction - physiology Thyroid thyroid hormone receptor Trans-Activators - metabolism Transcription, Genetic transcriptional repression Triiodothyronine - metabolism |
| title | The thyroid hormone receptor antagonizes CREB-mediated transcription |
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