首页> 中文期刊>中国科学技术大学学报 >CdCl2通过破坏PML-NBs结构和促进PML降解诱导细胞凋亡

CdCl2通过破坏PML-NBs结构和促进PML降解诱导细胞凋亡

     

摘要

PML-NBs (PML nuclear bodies) are kinetic structures that change significantly in number, size and position under cellular stress. For example, heat shock and heavy metals induce the disruption of PML-NBs into many small bodies. Similarly, DNA-damaging agents including Cisplatin and Alkylating result in the redistribution of PML-NBs into smaller dots or even into a diffuse mode. Although previous studies have tried to investigate those phenotypes, the function of PML microstructures under stress is still unknown. In our recent study, CdCl2 was used to treat Hela cells and it was found that PML-NBs were disrupted in the nucleus, and part of the PML protein was transferred into cytoplasm colocalizing with Ubquitin and then degraded. The ultimate effect of CdCl2 on Hela cells was to induce apoptosis. Our observations offer evidence to further understand the function of PML and PML-NBs, and may be helpful with screening drugs for APL chemotherapy.%PML核体(PML-NBs)是一种相对稳定的结构,但其数目、大小和位置在细胞压力下可发生显著改变.如热休克及重金属会导致PML-NBs裂解成数目众多的小点.DNA损伤试剂,如Cisplatin和Alkylating试剂也可导致PML-NBs分散成更小的小体,甚至呈现一种弥散的状态.虽然先前的研究试图解释这些压力状态下PML-NBs的表型变化,但其机制仍知之甚少.在最近的研究中,我们用CdCl2处理Hela细胞,发现PML-NBs的稳定结构遭到破坏而弥散在整个细胞核中,有趣的是,部分PML蛋白迁徙到胞浆之中并与泛素蛋白共定位,进而引起PML蛋白的降解,最终使得PML-NBs无法恢复而诱导细胞发生凋亡.本研究为进一步认识PML和PML-NBs的功能提供了证据,也将对化学治疗药物的筛选有所帮助.

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