XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling
A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independ...
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| Veröffentlicht in: | Molecular cell 2012-03, Vol.45 (5), p.619-628 |
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| creator | Hanson, Alison J. Wallace, Heather A. Freeman, Tanner J. Beauchamp, R. Daniel Lee, Laura A. Lee, Ethan |
| description | A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.
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► Screen identifies DIAP1 as a positive Wingless signaling regulator ► XIAP is required for Wnt signaling in mammalian cells and Xenopus embryos ► XIAP is recruited to TCF/Lef upon Wnt signaling and monoubiquitylates Groucho/TLE ► Ubiquitylation of TLE disrupts TCF binding to facilitate β-catenin-TCF interaction |
| doi_str_mv | 10.1016/j.molcel.2011.12.032 |
| format | Article |
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► Screen identifies DIAP1 as a positive Wingless signaling regulator ► XIAP is required for Wnt signaling in mammalian cells and Xenopus embryos ► XIAP is recruited to TCF/Lef upon Wnt signaling and monoubiquitylates Groucho/TLE ► Ubiquitylation of TLE disrupts TCF binding to facilitate β-catenin-TCF interaction</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2011.12.032</identifier><identifier>PMID: 22304967</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; apoptosis ; Co-Repressor Proteins - metabolism ; Drosophila ; Drosophila - genetics ; Drosophila - metabolism ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Drosophila Proteins - physiology ; Embryo, Nonmammalian - metabolism ; HEK293 Cells ; Humans ; Inhibitor of Apoptosis Proteins - genetics ; Inhibitor of Apoptosis Proteins - metabolism ; Inhibitor of Apoptosis Proteins - physiology ; mammals ; Models, Genetic ; repressor proteins ; RNA Interference ; transcription (genetics) ; Ubiquitination ; Wnt Proteins - metabolism ; Wnt Signaling Pathway ; Wnt1 Protein - metabolism ; X-Linked Inhibitor of Apoptosis Protein - genetics ; X-Linked Inhibitor of Apoptosis Protein - metabolism ; X-Linked Inhibitor of Apoptosis Protein - physiology ; Xenopus ; Xenopus Proteins - metabolism</subject><ispartof>Molecular cell, 2012-03, Vol.45 (5), p.619-628</ispartof><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-25b6408ca26f51573020ac561d1255c50e12a57270b2f23dec3f9a34847dcdc33</citedby><cites>FETCH-LOGICAL-c497t-25b6408ca26f51573020ac561d1255c50e12a57270b2f23dec3f9a34847dcdc33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276512000421$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22304967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanson, Alison J.</creatorcontrib><creatorcontrib>Wallace, Heather A.</creatorcontrib><creatorcontrib>Freeman, Tanner J.</creatorcontrib><creatorcontrib>Beauchamp, R. Daniel</creatorcontrib><creatorcontrib>Lee, Laura A.</creatorcontrib><creatorcontrib>Lee, Ethan</creatorcontrib><title>XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.
[Display omitted]
► Screen identifies DIAP1 as a positive Wingless signaling regulator ► XIAP is required for Wnt signaling in mammalian cells and Xenopus embryos ► XIAP is recruited to TCF/Lef upon Wnt signaling and monoubiquitylates Groucho/TLE ► Ubiquitylation of TLE disrupts TCF binding to facilitate β-catenin-TCF interaction</description><subject>Animals</subject><subject>apoptosis</subject><subject>Co-Repressor Proteins - metabolism</subject><subject>Drosophila</subject><subject>Drosophila - genetics</subject><subject>Drosophila - metabolism</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Drosophila Proteins - physiology</subject><subject>Embryo, Nonmammalian - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - genetics</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Inhibitor of Apoptosis Proteins - physiology</subject><subject>mammals</subject><subject>Models, Genetic</subject><subject>repressor proteins</subject><subject>RNA Interference</subject><subject>transcription (genetics)</subject><subject>Ubiquitination</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt Signaling Pathway</subject><subject>Wnt1 Protein - metabolism</subject><subject>X-Linked Inhibitor of Apoptosis Protein - genetics</subject><subject>X-Linked Inhibitor of Apoptosis Protein - metabolism</subject><subject>X-Linked Inhibitor of Apoptosis Protein - physiology</subject><subject>Xenopus</subject><subject>Xenopus Proteins - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERUvpP0CQW7lsOh5_JRekarWUSouo1Fb0ZnkdZ_EqiVs7Qeq_x6ssHFtfxodn3hnNQ8hHCiUFKi92ZR8667oSgdKSYgkM35ATCrVacCr528MflRTH5H1KOwDKRVW_I8eIDHgt1QlZPVxf3hQ_whCmjX-a_PjcmdGl4iqGyf4OF3frVTGG4iaGPoyuWJohDN6arvg1jMWt3w6m88P2AzlqTZfc2aGekvtvq7vl98X659X18nK9sLxW4wLFRnKorEHZCioUAwRjhaQNRSGsAEfRCIUKNtgia5xlbW0Yr7hqbGMZOyXnc-5jDE-TS6Pufco36MzgwpR0japiDEBm8suLJEJ-giJnr6IUoKo41GyfymfUxpBSdK1-jL438TlDem9F7_RsRe-taIo6W8ltnw4Tpk3vmv9N_zRk4PMMtCZos40-6fvbnCDzkoi03hNfZ8Ll8_7xLupkvRusa3x0dtRN8C_v8BfxqKXt</recordid><startdate>20120309</startdate><enddate>20120309</enddate><creator>Hanson, Alison J.</creator><creator>Wallace, Heather A.</creator><creator>Freeman, Tanner J.</creator><creator>Beauchamp, R. 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Daniel</au><au>Lee, Laura A.</au><au>Lee, Ethan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2012-03-09</date><risdate>2012</risdate><volume>45</volume><issue>5</issue><spage>619</spage><epage>628</epage><pages>619-628</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.
[Display omitted]
► Screen identifies DIAP1 as a positive Wingless signaling regulator ► XIAP is required for Wnt signaling in mammalian cells and Xenopus embryos ► XIAP is recruited to TCF/Lef upon Wnt signaling and monoubiquitylates Groucho/TLE ► Ubiquitylation of TLE disrupts TCF binding to facilitate β-catenin-TCF interaction</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22304967</pmid><doi>10.1016/j.molcel.2011.12.032</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals apoptosis Co-Repressor Proteins - metabolism Drosophila Drosophila - genetics Drosophila - metabolism Drosophila Proteins - genetics Drosophila Proteins - metabolism Drosophila Proteins - physiology Embryo, Nonmammalian - metabolism HEK293 Cells Humans Inhibitor of Apoptosis Proteins - genetics Inhibitor of Apoptosis Proteins - metabolism Inhibitor of Apoptosis Proteins - physiology mammals Models, Genetic repressor proteins RNA Interference transcription (genetics) Ubiquitination Wnt Proteins - metabolism Wnt Signaling Pathway Wnt1 Protein - metabolism X-Linked Inhibitor of Apoptosis Protein - genetics X-Linked Inhibitor of Apoptosis Protein - metabolism X-Linked Inhibitor of Apoptosis Protein - physiology Xenopus Xenopus Proteins - metabolism |
| title | XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling |
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