磷酸开关控制 RNF43 介导的 Wnt 受体降解以抑制肿瘤发生。,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

磷酸开关控制 RNF43 介导的 Wnt 受体降解以抑制肿瘤发生。
Nature Communications ( IF 14.7 ) Pub Date : 2020-09-15 , DOI: 10.1038/s41467-020-18257-3
Tadasuke Tsukiyama ₁ , Juqi Zou ₂ , Jihoon Kim _{3,

4} , Shohei Ogamino ₅ , Yuki Shino ₆ , Takamasa Masuda ₇ , Alessandra Merenda ₃ , Masaki Matsumoto _{8,

9} , Yoichiro Fujioka ₁₀ , Tomonori Hirose ₁₁ , Sayuri Terai ₁ , Hidehisa Takahashi _{1,

11} , Tohru Ishitani _{2,

5,

7} , Keiichi I Nakayama _{8,

12} , Yusuke Ohba ₁₀ , Bon-Kyoung Koo ₄ , Shigetsugu Hatakeyama ₁

Affiliation

Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Department of Homeostatic Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria.
Laboratory of Integrated Signaling Systems, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512, Japan.
Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Division of Proteomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Omics and Systems Biology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-douri, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Division of Cell Biology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

在许多癌症中观察到肿瘤抑制因子 RNF43 的频繁突变，尤其是结肠恶性肿瘤。RNF43 是一种 E3 泛素连接酶，通过诱导 Wnt 受体 Frizzled 降解来负调节 Wnt 信号传导。在这项研究中，我们发现 RNF43 活性需要在保守的丝氨酸三联体上进行磷酸化。RNF43 的这种磷酸化调节是斑马鱼发育和小鼠肠道类器官生长所必需的。消除 RNF43 磷酸化的癌症相关突变与活性 Ras 协同作用，通过消除 RNF43 在 Wnt 信号传导中的抑制功能同时保持其在 p53 信号传导中的抑制功能来促进肿瘤发生。我们的数据表明，RNF43 突变与 KRAS 突变合作，通过 Wnt-Ras-p53 轴在人类结肠癌中促进多步肿瘤发生。最后，丝氨酸三重组的磷模拟取代恢复了细胞外致癌突变体的肿瘤抑制活性。因此，利用 RNF43 的磷酸化调节可能是具有 RNF43 突变的肿瘤的潜在治疗策略。

"点击查看英文标题和摘要"

更新日期：2020-09-15

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南