A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor.
A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor.
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DOI：
10.1016/j.devcel.2006.05.004
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发表时间：
2006-06
影响因子：
11.8
通讯作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
中科院分区：
文献类型：
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作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
Ci/Gli 转录因子家族在许多关键发育过程中介导 Hedgehog (Hh) 信号传导。在这里，我们将 aHh 诱导的 MATH 和 BTB 结构域含有蛋白 (HIB) 鉴定为 Hh 通路的负调节因子。过表达 HIB 会下调 Ci 并阻断 Hh 信号传导，而灭活 HIB 会导致 Ci 积累并增强通路活性。 HIB 结合 Ci 的 N 端和 C 端区域，两者均介导 Ci 降解。 HIB 与 Cul3（模块化泛素连接酶的支架）形成复合物，并通过 Cul3 促进 Ci 泛素化和降解。此外，HIB 介导的 Ci 降解受 Hh 刺激并受 Fused 抑制剂 (Sufu) 抑制。 HIB的哺乳动物同源物SPOP可以在功能上替代HIB，并且Gli蛋白在果蝇中被HIB/SPOP降解。我们提供的证据表明，HIB 可以防止形态发生沟后的异常 Hh 信号传导，这对于正常的眼睛发育至关重要。
The Ci/Gli family of transcription factors mediates Hedgehog (Hh) signaling in many key developmental processes. Here we identify aHh-induced MATH andBTB domain containing protein (HIB) as a negative regulator of the Hh pathway. Overexpressing HIB downregulates Ci and blocks Hh signaling, whereas inactivating HIB results in Ci accumulation and enhanced pathway activity. HIB binds the N- and C-terminal regions of Ci, both of which mediate Ci degradation. HIB forms a complex with Cul3, a scaffold for modular ubiquitin ligases, and promotes Ci ubiquitination and degradation through Cul3. Furthermore, HIB-mediated Ci degradation is stimulated by Hh and inhibited by Suppressor of Fused (Sufu). The mammalian homolog of HIB, SPOP, can functionally substitute for HIB, and Gli proteins are degraded by HIB/SPOP inDrosophila. We provide evidence that HIB prevents aberrant Hh signaling posterior to the morphogenic furrow, which is essential for normal eye development.