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Tollip, an Intracellular Trafficking Protein, Is a Novel Modulator of the Transforming Growth Factor-beta Signaling Pathway
文献类型：期刊论文
| 作者 | Zhu, Lu; Wang, Lingdi; Luo, Xiaolin; Zhang, Yongxian（张永贤）; Ding, QiuRong（丁秋蓉） ; Jiang, Xiaomeng; Wang, Xiao; Pan, Yi（潘怡）; Chen, Yan（陈雁）
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2012 |
| 卷号 | 287期号:47页码:39653-39663 |
| 英文摘要 | Upon activation, TGF-beta type I receptor (T beta RI) undergoes active ubiquitination via recruitment of E3 ligases to the receptor complex by Smad7. However, how ubiquitination of T beta RI is coupled to intracellular trafficking, and protein degradation remains unclear. We report here that Tollip, an adaptor protein that contains both ubiquitin-associated domains and endosome-targeting domain, plays an important role in modulating trafficking and degradation of T beta RI. Tollip was previously demonstrated to possess a functional role in modulating the signaling of interleukin-1 and Toll-like receptors. We identify here that Tollip interacts with Smad7, a major modulatory protein involved in the negative regulation of TGF-beta signaling. Overexpression of Tollip antagonizes TGF-beta-stimulated transcriptional response, Smad2 phosphorylation, and epithelial-mesenchymal transition. Tollip also interacts with ubiquitinated T beta RI, and such interaction requires ubiquitin-associated domains of Tollip. The interaction and intracellular colocalization of Tollip with T beta RI is enhanced by Smad7. Overexpression of Tollip accelerates protein degradation of activated T beta RI. In addition, Tollip alters subcellular compartmentalization and endosomal trafficking of activated T beta RI. Collectively, our studies reveal that Tollip cooperates with Smad7 to modulate intracellular trafficking and degradation of ubiquitinated T beta RI, whereby negatively regulates TGF-beta signaling pathway. |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | IL-1 RECEPTOR ; KAPPA-B ; TGF ; UBIQUITIN ; INTERLEUKIN-1 ; SMAD7 ; ACTIVATION ; COMPLEX ; DOMAIN ; LIPOPOLYSACCHARIDE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000311233800035 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/64]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 |
| 推荐引用方式 GB/T 7714 | Zhu, Lu,Wang, Lingdi,Luo, Xiaolin,et al. Tollip, an Intracellular Trafficking Protein, Is a Novel Modulator of the Transforming Growth Factor-beta Signaling Pathway[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(47):39653-39663. |
| APA | Zhu, Lu.,Wang, Lingdi.,Luo, Xiaolin.,Zhang, Yongxian.,Ding, QiuRong.,...&Chen, Yan.(2012).Tollip, an Intracellular Trafficking Protein, Is a Novel Modulator of the Transforming Growth Factor-beta Signaling Pathway.JOURNAL OF BIOLOGICAL CHEMISTRY,287(47),39653-39663. |
| MLA | Zhu, Lu,et al."Tollip, an Intracellular Trafficking Protein, Is a Novel Modulator of the Transforming Growth Factor-beta Signaling Pathway".JOURNAL OF BIOLOGICAL CHEMISTRY 287.47(2012):39653-39663. |
入库方式： OAI收割
来源：上海营养与健康研究所
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