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...
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| Veröffentlicht in: | The Journal of biological chemistry 2001-10, Vol.276 (43), p.40113 |
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| container_issue | 43 |
| container_start_page | 40113 |
| container_title | The Journal of biological chemistry |
| container_volume | 276 |
| creator | Xianwang Meng Raymond Poon Xiaoyun Zhang Alexander Cheah Qi Ding Chi-chung Hui Benjamin Alman |
| 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 (APC mut ) 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 (APC mut ) 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 |
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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 (APC mut ) 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 (APC mut ) 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>American Society for Biochemistry and Molecular Biology</publisher><ispartof>The Journal of biological chemistry, 2001-10, Vol.276 (43), p.40113</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></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></links><search><creatorcontrib>Xianwang Meng</creatorcontrib><creatorcontrib>Raymond Poon</creatorcontrib><creatorcontrib>Xiaoyun Zhang</creatorcontrib><creatorcontrib>Alexander Cheah</creatorcontrib><creatorcontrib>Qi Ding</creatorcontrib><creatorcontrib>Chi-chung Hui</creatorcontrib><creatorcontrib>Benjamin Alman</creatorcontrib><title>Suppressor of Fused Negatively Regulates β-Catenin Signaling</title><title>The Journal of biological chemistry</title><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 (APC mut ) 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 (APC mut ) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates β-catenin signaling and that CRM-1-mediated
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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 (APC mut ) 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 (APC mut ) 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><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>11477086</pmid><doi>10.1074/jbc.M105317200</doi></addata></record> |
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| ispartof | The Journal of biological chemistry, 2001-10, Vol.276 (43), p.40113 |
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| title | Suppressor of Fused Negatively Regulates β-Catenin Signaling |
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