Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex
Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex
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DOI：
10.1073/pnas.082096999
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发表时间：
2002-04-16
影响因子：
11.1
通讯作者：
Bishop, JM
中科院分区：
文献类型：
--
作者：
Cheng, SY;Bishop, JM
Suppressor of Fused [Su（fu）]蛋白在调节Hedgehog（Hh）信号通路的Gli转录因子中起保守作用，Hh信号通路控制发育期间的细胞命运和组织模式。在果蝇和哺乳动物中，Su（fu）抑制Gli介导的转录，但其作用方式尚未完全了解。最近的证据表明，Su（fu）与Gli蛋白质物理相互作用，并且当过表达时，将Gli隔离在细胞质中。然而，Su（fu）也在丝氨酸-苏氨酸激酶Fused（Fu）的影响下穿过细胞核，并且具有与Gli形成DNA结合复合物的能力，这表明它具有核功能。在这里，我们报告说，苏（fu）[mSu（fu）]的小鼠同源物专门与SAP 18，一个组件的mSin 3和组蛋白脱乙酰酶复合物相互作用。此外，我们证明了mSu（fu）功能与SAP 18合作，通过将SAP 18-mSin 3复合物招募到含有Gli结合元件的启动子来抑制转录。这些结果为Su（fu）直接参与调控Gli转录活性提供了生化证据。
The Suppressor of Fused [Su(fu)] protein plays a conserved role in the regulation of Gli transcription factors of the hedgehog (Hh) signaling pathway that controls cell fate and tissue patterning during development. In both Drosophila and mammals, Su(fu) represses Gli-mediated transcription, but the mode of its action is not completely understood. Recent evidence suggests that Su(fu) physically interacts with the Gli proteins and, when overexpressed, sequesters Gli in the cytoplasm. However, Su(fu) also traverses into the nucleus under the influence of a serine-threonine kinase, Fused (Fu), and has the ability to form a DNA-binding complex with Gli, suggesting that it has a nuclear function. Here we report that the mouse homolog of Su(fu) [mSu(fu)] specifically interacts with SAP18, a component of the mSin3 and histone deacetylase complex. In addition, we demonstrate that mSu(fu) functionally cooperates with SAP18 to repress transcription by recruiting the SAP18-mSin3 complex to promoters containing the Gli-binding element. These results provide biochemical evidence that Su(fu) directly participates in modulating the transcriptional activity of Gli.