Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation.
Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation.
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DOI：
10.1016/j.devcel.2013.05.006
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发表时间：
2013-06
影响因子：
11.8
通讯作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
中科院分区：
文献类型：
--
作者：
Zhao Zhang;Xiangdong Lv;Wen-chi Yin;Xiaoyun Zhang;Jing Feng;Wenqing Wu;C. Hui;Lei Zhang;
Cubitus interruptus(Ci)/Gli转录因子家族可以被蛋白酶体完全或部分地从全长形式(Ci155/GliFL)降解为截短抑制因子(Ci75/Glir)，以介导Hedgehog(HH)信号转导。蛋白酶体区分泛素化的Ci/Gli进行完全降解和部分降解的机制尚不清楚。在这里，我们证明了Ter94 ATPase和它的哺乳动物对应的p97分别参与了将Ci和Gli3加工成Ci75和Gli3R的过程。Ter94通过其适配子Ufd1-like和dNpl4调节基于Cul1肢体的E3连接酶对泛素化Ci的部分降解。我们证明了基于Cul1的E3连接酶，而不是基于CUL3-RDX的E3连接酶，通过有效地添加K11连接的泛素链来修饰Ci。Ter94Ufd1-like/dNpl4复合体直接与Cul1-SLimb相互作用，有趣的是，它更喜欢K11连接的泛素化Ci。因此，Ter94 ATPase和K11连接的泛素化有助于蛋白酶体对部分降解的选择性。
The Cubitus interruptus (Ci)/Gli family of transcription factors can be degraded either completely or partially from a full-length form (Ci155/GliFL) to a truncated repressor (Ci75/GliR) by proteasomes to mediate Hedgehog (Hh) signaling. The mechanism by which proteasomes distinguish ubiquitinated Ci/Gli to carry out complete versus partial degradation is not known. Here, we show that Ter94 ATPase and its mammalian counterpart, p97, are involved in processing Ci and Gli3 into Ci75 and Gli3R, respectively. Ter94 regulates the partial degradation of ubiquitinated Ci by Cul1-Slimb-based E3 ligase through its adaptors Ufd1-like and dNpl4. We demonstrate that Cul1-Slimb-based E3 ligase, but not Cul3-Rdx-based E3 ligase, modifies Ci by efficient addition of K11-linked ubiquitin chains. Ter94Ufd1-like/dNpl4complex interacts directly with Cul1-Slimb, and, intriguingly, it prefers K11-linked ubiquitinated Ci. Thus, Ter94 ATPase and K11-linked ubiquitination in Ci contribute to the selectivity by proteasomes for partial degradation.