Suppressor of Fused Negatively Regulates β-Catenin Signaling
Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional a...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2001-10, Vol.276 (43), p.40113-40119 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 40119 |
|---|---|
| container_issue | 43 |
| container_start_page | 40113 |
| container_title | The Journal of biological chemistry |
| container_volume | 276 |
| creator | Meng, Xianwang Poon, Raymond Zhang, Xiaoyun Cheah, Alexander Ding, Qi Hui, Chi-chung Alman, Benjamin |
| description | Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator β-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APCmut) colon cancer cells in which β-catenin protein is stabilized leads to a reduction in nuclear β-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APCmut) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates β-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor. |
| doi_str_mv | 10.1074/jbc.M105317200 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72221351</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820600874</els_id><sourcerecordid>72221351</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-2e48cb81b07f65eab17e83e5908b4d36d75fd2b5a5820f3a1a1d9cc0aedb41d63</originalsourceid><addsrcrecordid>eNqFkE1Lw0AQhhdRbK1ePUpO3lJ3Nl_bgwcpVoWqYBW8LfsxCVvSJO4mhf4tf4i_yZQWehLfy8zhmRfmIeQS6BhoFt8slR4_A00iyBilR2QIlEdhlMDnMRlSyiCcsIQPyJn3S9onnsApGQDEWUZ5OiS3i65pHHpfu6DOg1nn0QQvWMjWrrHcBG9YdKVs0Qc_3-G0XypbBQtbVLK0VXFOTnJZerzYzxH5mN2_Tx_D-evD0_RuHuoYoA0ZxlwrDopmeZqgVJAhjzCZUK5iE6UmS3LDVCITzmgeSZBgJlpTiUbFYNJoRK53vY2rvzr0rVhZr7EsZYV150XGGIP-6X9B4NCHbcHxDtSu9t5hLhpnV9JtBFCxNSt6s-Jgtj-42jd3aoXmgO9V9gDfAdiLWFt0wmuLlUZjHepWmNr-1f0L302HPw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18111121</pqid></control><display><type>article</type><title>Suppressor of Fused Negatively Regulates β-Catenin Signaling</title><source>MEDLINE</source><source>Free E-Journal (出版社公開部分のみ）</source><source>Alma/SFX Local Collection</source><creator>Meng, Xianwang ; Poon, Raymond ; Zhang, Xiaoyun ; Cheah, Alexander ; Ding, Qi ; Hui, Chi-chung ; Alman, Benjamin</creator><creatorcontrib>Meng, Xianwang ; Poon, Raymond ; Zhang, Xiaoyun ; Cheah, Alexander ; Ding, Qi ; Hui, Chi-chung ; Alman, Benjamin</creatorcontrib><description>Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator β-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APCmut) colon cancer cells in which β-catenin protein is stabilized leads to a reduction in nuclear β-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APCmut) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates β-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M105317200</identifier><identifier>PMID: 11477086</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Active Transport, Cell Nucleus ; Animals ; Antibiotics, Antineoplastic - pharmacology ; b-catenin ; beta Catenin ; Carcinoma - genetics ; Carcinoma - metabolism ; Cell Compartmentation ; colon cancer ; Colonic Neoplasms - genetics ; Colonic Neoplasms - metabolism ; CRM1 protein ; Cytoskeletal Proteins - metabolism ; Exportin 1 Protein ; Fatty Acids, Unsaturated - pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; Karyopherins - antagonists & inhibitors ; leptomycin B ; Mice ; Mice, Nude ; Proto-Oncogene Proteins - metabolism ; Receptors, Cytoplasmic and Nuclear ; Repressor Proteins - metabolism ; Signal Transduction ; Su(fu) protein ; Suppressor Factors, Immunologic ; T-cell factor ; Tcf protein ; Trans-Activators ; Transcription Factors ; Tumor Cells, Cultured ; Wnt Proteins ; Zebrafish Proteins</subject><ispartof>The Journal of biological chemistry, 2001-10, Vol.276 (43), p.40113-40119</ispartof><rights>2001 © 2001 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-c411t-2e48cb81b07f65eab17e83e5908b4d36d75fd2b5a5820f3a1a1d9cc0aedb41d63</citedby><cites>FETCH-LOGICAL-c411t-2e48cb81b07f65eab17e83e5908b4d36d75fd2b5a5820f3a1a1d9cc0aedb41d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11477086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meng, Xianwang</creatorcontrib><creatorcontrib>Poon, Raymond</creatorcontrib><creatorcontrib>Zhang, Xiaoyun</creatorcontrib><creatorcontrib>Cheah, Alexander</creatorcontrib><creatorcontrib>Ding, Qi</creatorcontrib><creatorcontrib>Hui, Chi-chung</creatorcontrib><creatorcontrib>Alman, Benjamin</creatorcontrib><title>Suppressor of Fused Negatively Regulates β-Catenin Signaling</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator β-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APCmut) colon cancer cells in which β-catenin protein is stabilized leads to a reduction in nuclear β-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APCmut) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates β-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.</description><subject>Active Transport, Cell Nucleus</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>b-catenin</subject><subject>beta Catenin</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - metabolism</subject><subject>Cell Compartmentation</subject><subject>colon cancer</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - metabolism</subject><subject>CRM1 protein</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Exportin 1 Protein</subject><subject>Fatty Acids, Unsaturated - pharmacology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Karyopherins - antagonists & inhibitors</subject><subject>leptomycin B</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear</subject><subject>Repressor Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Su(fu) protein</subject><subject>Suppressor Factors, Immunologic</subject><subject>T-cell factor</subject><subject>Tcf protein</subject><subject>Trans-Activators</subject><subject>Transcription Factors</subject><subject>Tumor Cells, Cultured</subject><subject>Wnt Proteins</subject><subject>Zebrafish Proteins</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1Lw0AQhhdRbK1ePUpO3lJ3Nl_bgwcpVoWqYBW8LfsxCVvSJO4mhf4tf4i_yZQWehLfy8zhmRfmIeQS6BhoFt8slR4_A00iyBilR2QIlEdhlMDnMRlSyiCcsIQPyJn3S9onnsApGQDEWUZ5OiS3i65pHHpfu6DOg1nn0QQvWMjWrrHcBG9YdKVs0Qc_3-G0XypbBQtbVLK0VXFOTnJZerzYzxH5mN2_Tx_D-evD0_RuHuoYoA0ZxlwrDopmeZqgVJAhjzCZUK5iE6UmS3LDVCITzmgeSZBgJlpTiUbFYNJoRK53vY2rvzr0rVhZr7EsZYV150XGGIP-6X9B4NCHbcHxDtSu9t5hLhpnV9JtBFCxNSt6s-Jgtj-42jd3aoXmgO9V9gDfAdiLWFt0wmuLlUZjHepWmNr-1f0L302HPw</recordid><startdate>20011026</startdate><enddate>20011026</enddate><creator>Meng, Xianwang</creator><creator>Poon, Raymond</creator><creator>Zhang, Xiaoyun</creator><creator>Cheah, Alexander</creator><creator>Ding, Qi</creator><creator>Hui, Chi-chung</creator><creator>Alman, Benjamin</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20011026</creationdate><title>Suppressor of Fused Negatively Regulates β-Catenin Signaling</title><author>Meng, Xianwang ; Poon, Raymond ; Zhang, Xiaoyun ; Cheah, Alexander ; Ding, Qi ; Hui, Chi-chung ; Alman, Benjamin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-2e48cb81b07f65eab17e83e5908b4d36d75fd2b5a5820f3a1a1d9cc0aedb41d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>b-catenin</topic><topic>beta Catenin</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - metabolism</topic><topic>Cell Compartmentation</topic><topic>colon cancer</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - metabolism</topic><topic>CRM1 protein</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Exportin 1 Protein</topic><topic>Fatty Acids, Unsaturated - pharmacology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Karyopherins - antagonists & inhibitors</topic><topic>leptomycin B</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Receptors, Cytoplasmic and Nuclear</topic><topic>Repressor Proteins - metabolism</topic><topic>Signal Transduction</topic><topic>Su(fu) protein</topic><topic>Suppressor Factors, Immunologic</topic><topic>T-cell factor</topic><topic>Tcf protein</topic><topic>Trans-Activators</topic><topic>Transcription Factors</topic><topic>Tumor Cells, Cultured</topic><topic>Wnt Proteins</topic><topic>Zebrafish Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meng, Xianwang</creatorcontrib><creatorcontrib>Poon, Raymond</creatorcontrib><creatorcontrib>Zhang, Xiaoyun</creatorcontrib><creatorcontrib>Cheah, Alexander</creatorcontrib><creatorcontrib>Ding, Qi</creatorcontrib><creatorcontrib>Hui, Chi-chung</creatorcontrib><creatorcontrib>Alman, Benjamin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</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>Meng, Xianwang</au><au>Poon, Raymond</au><au>Zhang, Xiaoyun</au><au>Cheah, Alexander</au><au>Ding, Qi</au><au>Hui, Chi-chung</au><au>Alman, Benjamin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppressor of Fused Negatively Regulates β-Catenin Signaling</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2001-10-26</date><risdate>2001</risdate><volume>276</volume><issue>43</issue><spage>40113</spage><epage>40119</epage><pages>40113-40119</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator β-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APCmut) colon cancer cells in which β-catenin protein is stabilized leads to a reduction in nuclear β-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APCmut) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates β-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11477086</pmid><doi>10.1074/jbc.M105317200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2001-10, Vol.276 (43), p.40113-40119 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72221351 |
| source | MEDLINE; Free E-Journal (出版社公開部分のみ）; Alma/SFX Local Collection |
| subjects | Active Transport, Cell Nucleus Animals Antibiotics, Antineoplastic - pharmacology b-catenin beta Catenin Carcinoma - genetics Carcinoma - metabolism Cell Compartmentation colon cancer Colonic Neoplasms - genetics Colonic Neoplasms - metabolism CRM1 protein Cytoskeletal Proteins - metabolism Exportin 1 Protein Fatty Acids, Unsaturated - pharmacology Gene Expression Regulation, Neoplastic Humans Karyopherins - antagonists & inhibitors leptomycin B Mice Mice, Nude Proto-Oncogene Proteins - metabolism Receptors, Cytoplasmic and Nuclear Repressor Proteins - metabolism Signal Transduction Su(fu) protein Suppressor Factors, Immunologic T-cell factor Tcf protein Trans-Activators Transcription Factors Tumor Cells, Cultured Wnt Proteins Zebrafish Proteins |
| title | Suppressor of Fused Negatively Regulates β-Catenin Signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T11%3A42%3A00IST&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=Suppressor%20of%20Fused%20Negatively%20Regulates%20%CE%B2-Catenin%20Signaling&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Meng,%20Xianwang&rft.date=2001-10-26&rft.volume=276&rft.issue=43&rft.spage=40113&rft.epage=40119&rft.pages=40113-40119&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M105317200&rft_dat=%3Cproquest_cross%3E72221351%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18111121&rft_id=info:pmid/11477086&rft_els_id=S0021925820600874&rfr_iscdi=true |