PML与基因组稳定性

基因组稳定性同肿瘤的发生、发展密切相关，维护基因组稳定性对于细胞行使正常的生理功能是至关重要的.早幼粒细胞白血病蛋白PML(promyelocytic leukemia)主要借助分子中RBCC结构，同近50种有重要功能的蛋白相互作用而形成PML-NBs(PML nuclear bodies).PML-NBs是与核基质结合的、动态的、亚核多蛋白复合物，它作为区室化核结构(compartmentalized nuclear architecture)——染色质间区室(interchromatin compartment)的功能单位，满足了真核基因高层次表达调控模式的时空要求.最新的研究证明：PML是基因组稳定性“守门人”——p53分子的搭档分子，同样在基因组稳定性调控中发挥着重要的功能作用.它协同p53参与了DNA损伤反应所诱发的细胞凋亡，还可组织多种DNA修复分子参与DNA损伤修复，在DNA损伤反应中具有重要作用；此外，PML还通过调控aurora A的活性参与中心体复制检查点调控，借助调控survivin的表达参与有丝分裂纺锤体组装检查点调控，在染色体复制和细胞分裂中均显示了重要的调控作用.而当PML表达缺失或不足时则与多种肿瘤的发生、发展相关联，因此PML分子在维护基因组稳定性中具有重要功能作用，本文仅就相关的最新研究进展予以概述

Promyelocytic Leukemia(PML) Protein and Genomic Stability

Genomic stability is frequently associated with tumor genesis and progression. Maintaining genomic stability is very important for cells exerting their physiological functions. By it's RBCC domain, promyelocytic leukemia (PML)protein can interact with nearly 50 proteins to form PML nuclear bodies (PML-NBs) which are dynamic, sub-nuclear and multi-protein complex combined with nuclear matrix. As a function unit of interchromatin compartment belonging to compartmentalized nuclear architecture, PML can meet the time-space demands at high level of regulation of eukaryotic gene expression. Recent studies have shown that PML is a new partner of p53, as gatekeeper of genomic stability. It can cooperate with p53 to induce cell apoptosis in DNA damage response. And it can recruit several repair molecules to take part in DNA damage repair. Moreover, PML participates in centrosome duplication checkpoint by regulating aurora A activity and spindle-assembly checkpoint by regulating survivin expression. There fore, PML plays an important role in maintaining genomic stability by regulating cell apoptosis, DNA repair, chromosome duplication and mitosis. And loss or insufficiency of PML expression has been found in several tumors and carcinoma cells. All of those showed that PML may be a key molecule in maintaining genomic stability. Here, we review and discuss the recent development in research of the relationship between PML and genomic stability.