Integration of Runx and Smad Regulatory Signals at Transcriptionally Active Subnuclear Sites
Runx factors control lineage commitment and are transcriptional effectors of Smad signaling. Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-06, Vol.99 (12), p.8048-8053 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Zaidi, Sayyed K. Sullivan, Andrew J. van Wijnen, Andre J. Stein, Janet L. Stein, Gary S. Lian, Jane B. |
| description | Runx factors control lineage commitment and are transcriptional effectors of Smad signaling. Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation. We show that the integration of Runx and Smad signals is mediated by in situ interactions at specific foci within the nucleus. Activated Smads are directed to these subnuclear foci only in the presence of Runx proteins. Smad-Runx complexes are associated in situ with the nuclear matrix, and this association requires the intranuclear targeting signal of Runx factors. The convergence of Smad and Runx proteins at these sites supports transcription as reflected by BrUTP labeling and functional cooperativity between the proteins. Thus, Runx-mediated intranuclear targeting of Smads is critical for the integration of two distinct pathways essential for fetal development. |
| doi_str_mv | 10.1073/pnas.112664499 |
| format | Article |
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Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation. We show that the integration of Runx and Smad signals is mediated by in situ interactions at specific foci within the nucleus. Activated Smads are directed to these subnuclear foci only in the presence of Runx proteins. Smad-Runx complexes are associated in situ with the nuclear matrix, and this association requires the intranuclear targeting signal of Runx factors. The convergence of Smad and Runx proteins at these sites supports transcription as reflected by BrUTP labeling and functional cooperativity between the proteins. Thus, Runx-mediated intranuclear targeting of Smads is critical for the integration of two distinct pathways essential for fetal development.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.112664499</identifier><identifier>PMID: 12060751</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Amino Acid Substitution ; Animals ; Biological Sciences ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins - pharmacology ; Bone Neoplasms ; Cell lines ; Cell nucleus ; Cell Nucleus - physiology ; Cells ; Cellular biology ; Cellular immunity ; Core Binding Factor alpha Subunits ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Fluorescent antibody techniques ; Gene expression ; Genes ; HeLa Cells ; Humans ; Mammals ; Mutagenesis, Site-Directed ; Neoplasm Proteins ; Nuclear matrix ; Osteosarcoma ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; Proteins ; Rats ; Recombinant Proteins - metabolism ; Signal Transduction ; Smad5 Protein ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic - drug effects ; Transfection ; Transforming Growth Factor beta - pharmacology ; Tumor Cells, Cultured</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2002-06, Vol.99 (12), p.8048-8053</ispartof><rights>Copyright 1993-2002 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 11, 2002</rights><rights>Copyright © 2002, The National Academy of Sciences 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-acefcfc5126d0708961d74e3e57ed7f59ff11990f66af2b37352161b14e6be203</citedby><cites>FETCH-LOGICAL-c585t-acefcfc5126d0708961d74e3e57ed7f59ff11990f66af2b37352161b14e6be203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/99/12.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3058959$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3058959$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12060751$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zaidi, Sayyed K.</creatorcontrib><creatorcontrib>Sullivan, Andrew J.</creatorcontrib><creatorcontrib>van Wijnen, Andre J.</creatorcontrib><creatorcontrib>Stein, Janet L.</creatorcontrib><creatorcontrib>Stein, Gary S.</creatorcontrib><creatorcontrib>Lian, Jane B.</creatorcontrib><title>Integration of Runx and Smad Regulatory Signals at Transcriptionally Active Subnuclear Sites</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Runx factors control lineage commitment and are transcriptional effectors of Smad signaling. Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation. We show that the integration of Runx and Smad signals is mediated by in situ interactions at specific foci within the nucleus. Activated Smads are directed to these subnuclear foci only in the presence of Runx proteins. Smad-Runx complexes are associated in situ with the nuclear matrix, and this association requires the intranuclear targeting signal of Runx factors. The convergence of Smad and Runx proteins at these sites supports transcription as reflected by BrUTP labeling and functional cooperativity between the proteins. Thus, Runx-mediated intranuclear targeting of Smads is critical for the integration of two distinct pathways essential for fetal development.</description><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone Morphogenetic Proteins - pharmacology</subject><subject>Bone Neoplasms</subject><subject>Cell lines</subject><subject>Cell nucleus</subject><subject>Cell Nucleus - physiology</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>Cellular immunity</subject><subject>Core Binding Factor alpha Subunits</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Fluorescent antibody techniques</subject><subject>Gene expression</subject><subject>Genes</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Mammals</subject><subject>Mutagenesis, Site-Directed</subject><subject>Neoplasm Proteins</subject><subject>Nuclear matrix</subject><subject>Osteosarcoma</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>Proteins</subject><subject>Rats</subject><subject>Recombinant Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Smad5 Protein</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transfection</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Tumor Cells, Cultured</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c1v0zAYBnALgVgZXDkhFHGAU8r7-iOJDxymiY9Jk5DWcUOyHMcuqVyn2M60_vckaimDAycf3t_jr4eQlwhLhJq93wWdloi0qjiX8hFZIEgsKy7hMVkA0LpsOOVn5FlKGwCQooGn5AwpVFALXJDvVyHbddS5H0IxuOJmDPeFDl2x2uquuLHr0es8xH2x6tdB-1ToXNxGHZKJ_W4Oae_3xYXJ_Z0tVmMbRuOtjhPPNj0nT9yUsS-O6zn59unj7eWX8vrr56vLi-vSiEbkUhvrjDNiekUHNTSywq7mlllR2652QjqHKCW4qtKOtqxmgmKFLXJbtZYCOycfDvvuxnZrO2NDjtqrXey3Ou7VoHv19yT0P9R6uFNIGWAz5d8e83H4OdqU1bZPxnqvgx3GpLDhAJzN8M0_cDOMcf4XRQGZBKQzWh6QiUNK0brTRRDUXJqaS1On0qbA64fX_8OPLT0Ac_D3WMpJqAb4fOS7_wLlRu-zvc-TfHWQmzTVeqIMRCOFZL8AxTW1jA</recordid><startdate>20020611</startdate><enddate>20020611</enddate><creator>Zaidi, Sayyed K.</creator><creator>Sullivan, Andrew J.</creator><creator>van Wijnen, Andre J.</creator><creator>Stein, Janet L.</creator><creator>Stein, Gary S.</creator><creator>Lian, Jane B.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><general>The National Academy of Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20020611</creationdate><title>Integration of Runx and Smad Regulatory Signals at Transcriptionally Active Subnuclear Sites</title><author>Zaidi, Sayyed K. ; 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Genetic defects in these pathways interfere with normal development. The in situ localization of Runx and Smad proteins must impact the mechanisms by which these proteins function together in gene regulation. We show that the integration of Runx and Smad signals is mediated by in situ interactions at specific foci within the nucleus. Activated Smads are directed to these subnuclear foci only in the presence of Runx proteins. Smad-Runx complexes are associated in situ with the nuclear matrix, and this association requires the intranuclear targeting signal of Runx factors. The convergence of Smad and Runx proteins at these sites supports transcription as reflected by BrUTP labeling and functional cooperativity between the proteins. Thus, Runx-mediated intranuclear targeting of Smads is critical for the integration of two distinct pathways essential for fetal development.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>12060751</pmid><doi>10.1073/pnas.112664499</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution Animals Biological Sciences Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins - pharmacology Bone Neoplasms Cell lines Cell nucleus Cell Nucleus - physiology Cells Cellular biology Cellular immunity Core Binding Factor alpha Subunits DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Fluorescent antibody techniques Gene expression Genes HeLa Cells Humans Mammals Mutagenesis, Site-Directed Neoplasm Proteins Nuclear matrix Osteosarcoma Phosphoproteins - genetics Phosphoproteins - metabolism Proteins Rats Recombinant Proteins - metabolism Signal Transduction Smad5 Protein Trans-Activators - genetics Trans-Activators - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic - drug effects Transfection Transforming Growth Factor beta - pharmacology Tumor Cells, Cultured |
| title | Integration of Runx and Smad Regulatory Signals at Transcriptionally Active Subnuclear Sites |
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