早幼粒细胞白血病(PML)核体,细胞核中的无膜细胞器,在细胞稳态中起着至关重要的作用。这些动态结构由支架PML蛋白和各种配偶体的组装产生。最近的晶体结构分析揭示了必要的自相互作用域,而液-液相分离有助于它们的形成。PML主体协调翻译后修饰,特别是应激诱导的SUMO化,影响靶蛋白功能。作为多个信号通路的枢纽,它们影响衰老等细胞过程。PML表达失调会导致疾病,包括癌症,强调其意义。治疗学上,PML机构是有希望的目标,以三氧化二砷和维甲酸恢复PML体成功治疗急性早幼粒细胞白血病为例。了解它们的功能可以阐明正常和病理的细胞生理学,指导潜在的疗法。这篇综述探讨了PML体内生物发生的最新进展,生化活性,以及它们不断演变的生物学角色。
Promyelocytic leukemia (PML) nuclear bodies, membrane-less organelles in the nucleus, play a crucial role in cellular homeostasis. These dynamic structures result from the assembly of scaffolding PML proteins and various partners. Recent crystal structure analyses revealed essential self-interacting domains, while liquid-liquid phase separation contributes to their formation. PML bodies orchestrate post-translational modifications, particularly stress-induced SUMOylation, impacting target protein functions. Serving as hubs in multiple signaling pathways, they influence cellular processes like senescence. Dysregulation of PML expression contributes to diseases, including cancer, highlighting their significance. Therapeutically, PML bodies are promising targets, exemplified by successful acute promyelocytic leukemia treatment with arsenic trioxide and retinoic acid restoring PML bodies. Understanding their functions illuminates both normal and pathological cellular physiology, guiding potential therapies. This review explores recent advancements in PML body biogenesis, biochemical activity, and their evolving biological roles.