UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing
UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing
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UbcD1 通过直接调节 Ci 泛素化和加工来调节 Hedgehog 信号传导
DOI：
10.15252/embr.201643289
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发表时间：
2017-09
期刊：
影响因子：
7.7
通讯作者：
Zhao Yun
中科院分区：
文献类型：
--
作者：
Pan Chenyu;Xiong Yue;Lv Xiangdong;Xia Yuanxin;Zhang Shuo;Chen Hao;Fan Jialin;Wu Wenqing;Liu Feng;Wu Hailong;Zhou Zhaocai;Zhang Lei;Zhao Yun
Hh通路控制后生动物中的许多形态发生过程，并在许多病理学和癌症中起重要作用。Hh信号传导由转录因子Gli/Ci家族的活性介导。果蝇中的几项研究表明，泛素E3连接酶Slimb和Rdx（Hib）的泛素化在控制依赖于Hh信号水平的Ci稳定性中起着至关重要的作用。如果Hh水平较低，Slimb会在Ci上添加K11-和K48-连接的聚遍在蛋白链，导致部分降解。泛素E2酶是决定泛素链拓扑结构的关键。然而，哪些E2酶参与了Ci的选择性泛素化降解仍然是难以捉摸的。在这里，我们发现，E2酶UbcD 1负调节Hh信号活性在果蝇翅盘。在翅盘和培养的细胞中的遗传和生化分析表明，UbcD 1直接控制Ci的稳定性。有趣的是，UbcD 1被发现选择性地参与Slimb介导的Ci降解。最后，我们表明，同源的UbcD 1在调节Hh信号在脊椎动物中发挥保守的作用。
The Hh pathway controls many morphogenetic processes in metazoans and plays important roles in numerous pathologies and in cancer. Hh signaling is mediated by the activity of the Gli/Ci family of transcription factors. Several studies in Drosophila have shown that ubiquitination by the ubiquitin E3 ligases Slimb and Rdx(Hib) plays a crucial role in controlling Ci stability dependent on the levels of Hh signals. If Hh levels are low, Slimb adds K11‐ and K48‐linked poly‐ubiquitin chains on Ci resulting in partial degradation. Ubiquitin E2 enzymes are pivotal in determining the topologies of ubiquitin chains. However, which E2 enzymes participate in the selective ubiquitination‐degradation of Ci remains elusive. Here, we find that the E2 enzyme UbcD1 negatively regulates Hh signaling activity in Drosophila wing disks. Genetic and biochemical analyses in wing disks and in cultured cells reveal that UbcD1 directly controls Ci stability. Interestingly, UbcD1 is found to be selectively involved in Slimb‐mediated Ci degradation. Finally, we show that the homologs of UbcD1 play a conserved role in modulating Hh signaling in vertebrates.
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影响因子：
11.8
作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
通讯作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
影响因子：
11.8
作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
通讯作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
DOI：
--
发表时间：
2006
影响因子：
11.1
作者：
Baolin Wang;Yanyun Li
通讯作者：
Baolin Wang;Yanyun Li
影响因子：
5.7
作者：
Sakata, Eri;Satoh, Tadashi;Kato, Koichi
通讯作者：
Kato, Koichi
影响因子：
2.7
作者：
J. Odenthal;F. V. Eeden;P. Haffter;P. Ingham;C. Nüsslein-Volhard
通讯作者：
J. Odenthal;F. V. Eeden;P. Haffter;P. Ingham;C. Nüsslein-Volhard