南方科技大学生命科学学院,深圳 518055
国家自然科学基金(32270831, 91853129), 广东省自然科 学基金(2023A1515012590) , 深圳市自然科学基金 (JCYJ20220530114802006),广东省科学技术厅(2022A1515010830) 和深圳市政府科技创新委员会(KQTD20200820113040070) 资助项目。
College of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
This work was supported by grants from The National Natural Science Foundation of China (32270831, 91853129), Natural Science Foundation of Guangdong Province (2023A1515012590), Natural Science Foundation of Shenzhen (JCYJ20220530114802006), Department of Science and Technology Agency of Guangdong Province (2022A1515010830), and Shenzhen Science and Technology Innovation Commission (KQTD20200820113040070).
COP1 E3泛素连接酶最初是在植物中作为光形态建成的关键抑制因子被发现和广泛研究的,是植物生长发育和环境适应过程中的核心“开关”。光受体接收外界环境信号后传递给COP1,COP1再靶向调控下游核心转录因子,从而完成光形态建成等生命过程。在哺乳动物中,尽管大部分光受体都消失,但COP1仍在代谢调控和肿瘤发生过程中靶向重要的转录因子。通过比较动植物中COP1调控过程的异同发现,哺乳动物中COP1所感知的上游信号几乎是未知的,其中COP1结合CRL4形成的复合体E3泛素连接酶的组装机制调控仍不清楚。植物中光是其主要能量来源和COP1的主要上游信号,而作为动物的主要能量来源,葡萄糖和相关激素很可能也是动物COP1的上游信号。同时,通过总结医学研究中针对蛋白质泛素化相关过程的丰富靶点和相关药物,可以为植物COP1等E3泛素连接酶的研究提供有效工具。COP1在细胞生命过程调控中至关重要,其功能和作用机制随着进化而产生多样性,尚有待继续深入探究。
COP1 is a RING E3 ligase first identified in plants, where it is instrumental in establishing photomorphogenesis. A complex regulatory network centered around COP1 has since been demonstrated to constitute a major signal transduction axis mediating light/darkness or temperature response, whereby changes in COP1 activity link light sensor modules (cryptochrome, phytochrome, UVR8, etc.) to core transcription factors (HY5, PIF, etc.) to reprogram cellular metabolism and growth response. While the photoreception network does not serve to orchestrate energy production in animals, mammalian COP1 is still critical in regulating metabolism and cell growth during tumorigenesis. In this review, we summarize currently known COP1 functions in animals v.s. plants. It can be seen that the stimuli sensed by mammalian COP1 and the signal transduction pathway there of remain largely unknown. Sunlight acts as both major energy source and an upstream signal of COP1 in plants. Similarly, glucose, the major energy source for animals, maybe highly correlated with COP1 upstream signaling. In both organisms, COP1 may respond to stimuli by altered localization, activity or assembly into super-E3 complex with CRL4, which remains to be further understood. Nonetheless, pharmacological studies on animal COP1 points to therapeutic directions, while also providing tools for further research on this enigmatic E3. COP1 is of vital importance in the regulation of cellular life process. Its has diverse function and mechanism through evolution, which needs to be further explored.
周璐,饶枫.动植物中COP1泛素连接酶介导的信号转导与蛋白质稳态调控[J].生物化学与生物物理进展,2023,50(4):714-724
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