形态原诱导的激酶凝聚物通过异质激活Gli来转化Hh信号
Yuhong Han1, Mengmeng Zhou1, Bing Wang1
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science advances
|January 10, 2025
概括
刺 (Hh) 信号使用化 (Fu) / Ulk 激酶形成生物分子凝聚物. 这些凝结物以异质激活Ci/Gli转录因子,控制胚胎发育和组织平衡.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 刺 (Hh) 形态通路对于胚胎发育和组织平衡至关重要.
- 这一途径是由Ci/Gli家族的转录因子调节的.
研究的目的:
- 阐明Hh信号调节Ci/Gli转录因子的机制.
- 研究化 (Fu) /Ulk激酶在Hh通路激活中的作用.
- 探索生物分子凝聚在信号传导中的功能.
主要方法:
- 研究了Fu/Ulk3激酶的Hh诱导酸化和SUMOylation.
- 分析了Fu/Ulk3在生物分子凝聚物中的自我组装.
- 检查了Ci-Sufu和Gli-Sufu复合物的这些凝结物的招募.
- 评估了凝结物中Fu/Ulk3的构造变化和激活.
- 量化了激活的Ci/Gli转录复合物的核积累.
主要成果:
- Hh信号诱导了Fu/Ulk3的酸化,促进了SUMOylation.
- SUMOylation驱动Fu/Ulk3自组装成为生物分子凝聚物.
- 这些凝结物招募细胞质Ci-Sufu和状Gli-Sufu.
- 在凝结物中,Fu/Ulk3经历着形状变化,激活了Ci/Gli.
- 激活的Ci/Gli以剂量和时间依赖的方式积聚在细胞核中.
结论:
- Hh信号利用Fu/Ulk激酶的生物分子凝聚,以全质调节Ci/Gli活动.
- 这种机制提供了对Hh信号传导的时空控制.
- 生物分子凝结作为一种新的调节机制,用于酶介导的信号传输.
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