Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus
Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/β-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/β-catenin signaling in chondrocyte di...
Saved in:
| Published in: | The Journal of biological chemistry 2009-01, Vol.284 (5), p.3323-3333 |
|---|---|
| Main Authors: | , , , , |
| Format: | Article |
| Language: | eng |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| recordid |
cdi_proquest_miscellaneous_66851231 |
|---|---|
| title |
Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus |
| format |
Article |
| creator |
Topol, Lilia Chen, Wen Song, Hai Day, Timothy F. Yang, Yingzi |
| subjects |
Animals Base Sequence beta Catenin - metabolism Blotting, Western Cell Line Cell Nucleus - metabolism DNA Primers Fluorescent Antibody Technique, Indirect Glycogen Synthase Kinase 3 - chemistry Glycogen Synthase Kinase 3 - metabolism Humans Immunoprecipitation Mice Phosphorylation Protein Transport Signal Transduction - physiology SOX9 Transcription Factor - physiology Transducin - chemistry Transducin - metabolism Wnt Proteins - metabolism |
| ispartof |
The Journal of biological chemistry, 2009-01, Vol.284 (5), p.3323-3333 |
| description |
Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/β-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/β-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/β-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote β-catenin degradation, whereas the C terminus is required to inhibit β-catenin transcriptional activity without affecting its stability. Sox9 binds to β-catenin and components of the β-catenin “destruction complex,” glycogen synthase kinase 3 and β-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance β-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient β-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by β-catenin. |
| language |
eng |
| source |
BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS; Open Access: PubMed Central; AUTh Library subscriptions: Elsevier ScienceDirect Journals |
| identifier |
ISSN: 0021-9258 |
| fulltext |
fulltext |
| issn |
0021-9258 1083-351X |
| url |
http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-05-27T20%3A51%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sox9%20Inhibits%20Wnt%20Signaling%20by%20Promoting%20%CE%B2-Catenin%20Phosphorylation%20in%20the%20Nucleus&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Topol,%20Lilia&rft.date=2009-01-30&rft.volume=284&rft.issue=5&rft.spage=3323&rft.epage=3333&rft.pages=3323-3333&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M808048200&rft_dat=%3Cproquest_cross%3E66851231%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c406t-955e30d7929314c004077b45e57e6a158332d2493224d269e3e05125b7edeb6e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=66851231&rft_id=info:pmid/19047045 |
| container_title |
The Journal of biological chemistry |
| container_volume |
284 |
| container_issue |
5 |
| container_start_page |
3323 |
| container_end_page |
3333 |
| fullrecord |
<record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66851231</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925819818963</els_id><sourcerecordid>66851231</sourcerecordid><originalsourceid>FETCH-LOGICAL-c406t-955e30d7929314c004077b45e57e6a158332d2493224d269e3e05125b7edeb6e3</originalsourceid><addsrcrecordid>eNp1kM1uEzEQgC1ERUPhyhH2xG3T8d_u-ogiKJVKqQgV3Cyvd5K42tip7UXNa_EgPBOuEqmnzmU0o29-9BHyjsKcQivO73o7_9ZBB6JjAC_IjELHay7p75dkBsBorZjsTsnrlO6ghFD0FTmlCkQLQs7Ij2V4UNWl37je5VT98rlaurU3o_Prqt9XNzFsQ34s_v2tFyajd7662YS024S4H012wVellTdYXU92xCm9IScrMyZ8e8xn5PbL55-Lr_XV94vLxaer2gpocq2kRA5Dq5jiVNjyGrRtLyTKFhtDZcc5G5hQnDExsEYhR5CUyb7FAfsG-Rn5eNi7i-F-wpT11iWL42g8hinppukKz2kB5wfQxpBSxJXeRbc1ca8p6EeLuljUTxbLwPvj5qnf4vCEH7UV4MMBWJmgzTq6pG-XDCiH8rcE1RaiOxBYDPxxGHWyDr3FwUW0WQ_BPXf9PxgciLw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><isCDI>true</isCDI><recordtype>article</recordtype><pqid>66851231</pqid></control><display><type>article</type><title>Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus</title><source>BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS</source><source>Open Access: PubMed Central</source><source>AUTh Library subscriptions: Elsevier ScienceDirect Journals</source><creator>Topol, Lilia ; Chen, Wen ; Song, Hai ; Day, Timothy F. ; Yang, Yingzi</creator><creatorcontrib>Topol, Lilia ; Chen, Wen ; Song, Hai ; Day, Timothy F. ; Yang, Yingzi</creatorcontrib><description>Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/β-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/β-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/β-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote β-catenin degradation, whereas the C terminus is required to inhibit β-catenin transcriptional activity without affecting its stability. Sox9 binds to β-catenin and components of the β-catenin “destruction complex,” glycogen synthase kinase 3 and β-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance β-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient β-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by β-catenin.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M808048200</identifier><identifier>PMID: 19047045</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Base Sequence ; beta Catenin - metabolism ; Blotting, Western ; Cell Line ; Cell Nucleus - metabolism ; DNA Primers ; Fluorescent Antibody Technique, Indirect ; Glycogen Synthase Kinase 3 - chemistry ; Glycogen Synthase Kinase 3 - metabolism ; Humans ; Immunoprecipitation ; Mice ; Phosphorylation ; Protein Transport ; Signal Transduction - physiology ; SOX9 Transcription Factor - physiology ; Transducin - chemistry ; Transducin - metabolism ; Wnt Proteins - metabolism</subject><ispartof>The Journal of biological chemistry, 2009-01, Vol.284 (5), p.3323-3333</ispartof><rights>2009 © 2009 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-955e30d7929314c004077b45e57e6a158332d2493224d269e3e05125b7edeb6e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021925819818963$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,787,791,3569,27985,27986,46162</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19047045$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Topol, Lilia</creatorcontrib><creatorcontrib>Chen, Wen</creatorcontrib><creatorcontrib>Song, Hai</creatorcontrib><creatorcontrib>Day, Timothy F.</creatorcontrib><creatorcontrib>Yang, Yingzi</creatorcontrib><title>Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/β-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/β-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/β-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote β-catenin degradation, whereas the C terminus is required to inhibit β-catenin transcriptional activity without affecting its stability. Sox9 binds to β-catenin and components of the β-catenin “destruction complex,” glycogen synthase kinase 3 and β-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance β-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient β-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by β-catenin.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>beta Catenin - metabolism</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>DNA Primers</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Glycogen Synthase Kinase 3 - chemistry</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Mice</subject><subject>Phosphorylation</subject><subject>Protein Transport</subject><subject>Signal Transduction - physiology</subject><subject>SOX9 Transcription Factor - physiology</subject><subject>Transducin - chemistry</subject><subject>Transducin - metabolism</subject><subject>Wnt Proteins - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp1kM1uEzEQgC1ERUPhyhH2xG3T8d_u-ogiKJVKqQgV3Cyvd5K42tip7UXNa_EgPBOuEqmnzmU0o29-9BHyjsKcQivO73o7_9ZBB6JjAC_IjELHay7p75dkBsBorZjsTsnrlO6ghFD0FTmlCkQLQs7Ij2V4UNWl37je5VT98rlaurU3o_Prqt9XNzFsQ34s_v2tFyajd7662YS024S4H012wVellTdYXU92xCm9IScrMyZ8e8xn5PbL55-Lr_XV94vLxaer2gpocq2kRA5Dq5jiVNjyGrRtLyTKFhtDZcc5G5hQnDExsEYhR5CUyb7FAfsG-Rn5eNi7i-F-wpT11iWL42g8hinppukKz2kB5wfQxpBSxJXeRbc1ca8p6EeLuljUTxbLwPvj5qnf4vCEH7UV4MMBWJmgzTq6pG-XDCiH8rcE1RaiOxBYDPxxGHWyDr3FwUW0WQ_BPXf9PxgciLw</recordid><startdate>20090130</startdate><enddate>20090130</enddate><creator>Topol, Lilia</creator><creator>Chen, Wen</creator><creator>Song, Hai</creator><creator>Day, Timothy F.</creator><creator>Yang, Yingzi</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>7X8</scope></search><sort><creationdate>20090130</creationdate><title>Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus</title><author>Topol, Lilia ; Chen, Wen ; Song, Hai ; Day, Timothy F. ; Yang, Yingzi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-955e30d7929314c004077b45e57e6a158332d2493224d269e3e05125b7edeb6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>beta Catenin - metabolism</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>DNA Primers</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Glycogen Synthase Kinase 3 - chemistry</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Mice</topic><topic>Phosphorylation</topic><topic>Protein Transport</topic><topic>Signal Transduction - physiology</topic><topic>SOX9 Transcription Factor - physiology</topic><topic>Transducin - chemistry</topic><topic>Transducin - metabolism</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Topol, Lilia</creatorcontrib><creatorcontrib>Chen, Wen</creatorcontrib><creatorcontrib>Song, Hai</creatorcontrib><creatorcontrib>Day, Timothy F.</creatorcontrib><creatorcontrib>Yang, Yingzi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Topol, Lilia</au><au>Chen, Wen</au><au>Song, Hai</au><au>Day, Timothy F.</au><au>Yang, Yingzi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2009-01-30</date><risdate>2009</risdate><volume>284</volume><issue>5</issue><spage>3323</spage><epage>3333</epage><pages>3323-3333</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/β-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/β-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/β-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote β-catenin degradation, whereas the C terminus is required to inhibit β-catenin transcriptional activity without affecting its stability. Sox9 binds to β-catenin and components of the β-catenin “destruction complex,” glycogen synthase kinase 3 and β-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance β-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient β-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by β-catenin.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19047045</pmid><doi>10.1074/jbc.M808048200</doi><oa>free_for_read</oa></addata></record> |