Groucho suppresses Pax2 transactivation by inhibition of JNK‐mediated phosphorylation
Pax proteins are DNA‐binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The Pax2 gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hind...
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| creator | Cai, Yi Brophy, Patrick D. Levitan, Inna Stifani, Stefano Dressler, Gregory R. |
| description | Pax proteins are DNA‐binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The
Pax2
gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c‐Jun N‐terminal kinase (JNK) to enhance Pax2‐dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator. |
| doi_str_mv | 10.1093/emboj/cdg536 |
| format | Article |
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Pax2
gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c‐Jun N‐terminal kinase (JNK) to enhance Pax2‐dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/cdg536</identifier><identifier>PMID: 14532124</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amino Acid Substitution ; Basic Helix-Loop-Helix Transcription Factors ; Binding Sites ; Cell Line ; c‐Jun ; Deoxyribonucleic acid ; DNA ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; EMBO09 ; EMBO11 ; Embryonic growth stage ; Grg4 protein ; Groucho ; Groucho protein ; Humans ; JNK Mitogen-Activated Protein Kinases ; Kidney ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - metabolism ; Multigene Family ; Mutagenesis, Site-Directed ; N‐terminal kinase ; Pax2 ; Pax2 protein ; PAX2 Transcription Factor ; Phosphorylation ; Plasmids ; Repressor Proteins - metabolism ; Suppression, Genetic ; TLE protein ; Transcription Factors - genetics ; transcription repression ; Transcription, Genetic ; Transfection</subject><ispartof>The EMBO journal, 2003-10, Vol.22 (20), p.5522-5529</ispartof><rights>European Molecular Biology Organization 2003</rights><rights>Copyright © 2003 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Oct 15, 2003</rights><rights>Copyright © 2003 European Molecular Biology Organization 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC213790/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC213790/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1093/emboj/cdg536$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14532124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Yi</creatorcontrib><creatorcontrib>Brophy, Patrick D.</creatorcontrib><creatorcontrib>Levitan, Inna</creatorcontrib><creatorcontrib>Stifani, Stefano</creatorcontrib><creatorcontrib>Dressler, Gregory R.</creatorcontrib><title>Groucho suppresses Pax2 transactivation by inhibition of JNK‐mediated phosphorylation</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Pax proteins are DNA‐binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The
Pax2
gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c‐Jun N‐terminal kinase (JNK) to enhance Pax2‐dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator.</description><subject>Amino Acid Substitution</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>c‐Jun</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>EMBO09</subject><subject>EMBO11</subject><subject>Embryonic growth stage</subject><subject>Grg4 protein</subject><subject>Groucho</subject><subject>Groucho protein</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>Kidney</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Multigene Family</subject><subject>Mutagenesis, Site-Directed</subject><subject>N‐terminal kinase</subject><subject>Pax2</subject><subject>Pax2 protein</subject><subject>PAX2 Transcription Factor</subject><subject>Phosphorylation</subject><subject>Plasmids</subject><subject>Repressor Proteins - metabolism</subject><subject>Suppression, Genetic</subject><subject>TLE protein</subject><subject>Transcription Factors - genetics</subject><subject>transcription repression</subject><subject>Transcription, 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J</stitle><addtitle>EMBO J</addtitle><date>2003-10-15</date><risdate>2003</risdate><volume>22</volume><issue>20</issue><spage>5522</spage><epage>5529</epage><pages>5522-5529</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Pax proteins are DNA‐binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The
Pax2
gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c‐Jun N‐terminal kinase (JNK) to enhance Pax2‐dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14532124</pmid><doi>10.1093/emboj/cdg536</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution Basic Helix-Loop-Helix Transcription Factors Binding Sites Cell Line c‐Jun Deoxyribonucleic acid DNA DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism EMBO09 EMBO11 Embryonic growth stage Grg4 protein Groucho Groucho protein Humans JNK Mitogen-Activated Protein Kinases Kidney Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Multigene Family Mutagenesis, Site-Directed N‐terminal kinase Pax2 Pax2 protein PAX2 Transcription Factor Phosphorylation Plasmids Repressor Proteins - metabolism Suppression, Genetic TLE protein Transcription Factors - genetics transcription repression Transcription, Genetic Transfection |
| title | Groucho suppresses Pax2 transactivation by inhibition of JNK‐mediated phosphorylation |
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