文章：

核微环境在生物控制和癌症中的应用

Nuclear microenvironments in biological control and cancer

原文发布日期：2007-06-01

DOI: 10.1038/nrc2149

类型: Review Article

开放获取: 否

要点：

1. The biological control of gene expression requires the temporal and spatial integration of dynamic processes. These include nuclear import, intranuclear targeting and chromatin remodelling that facilitate the organization and assembly of gene-regulatory machinery in microenvironments within the cell nucleus.
2. Combinatorial assembly and organization of nuclear microenvironments is mediated by scaffolding proteins at several sites in target gene promoters as well as in subnuclear domains. Such focal compartmentalization of regulatory machinery in nuclear microenvironments might regulate the dynamic formation and activity of physiologically responsive regulatory networks and provide threshold concentrations of factors that govern the extent to which genes are activated, suppressed or coordinately controlled.
3. Targeting of scaffolding proteins to specific sites within the nucleus supports their involvement in biological control and reflects the potential influence of cancer-related alterations on gene expression.
4. Solid tumours, leukaemias and lymphomas show striking alterations in nuclear morphology as well as in the architectural organization of genes, transcripts and regulatory complexes within the nucleus. Examples of altered nuclear microenvironments include promyelocytic leukaemia (PML) bodies and acute myeloid leukaemia (AML) foci in leukaemias, the nucleolus in some solid tumours and extensive chromosomal rearrangements.
5. Imaging principal nuclear compartments that are frequently rearranged in cancer combined with genomic and proteomic analyses can improve the biological and clinical relevance of regulatory signatures produced as a result of high throughput gene profiling of tumours.
6. Mechanistic insights into the temporal and spatial organization of the nuclear machinery involved in gene expression, which is compromised in tumours, provide a novel platform for diagnosis and therapy.

要点翻译：

1. 基因表达的生物调控需要动态过程在时间和空间上的整合。这些过程包括核输入、核内靶向和染色质重塑，这些过程促进了细胞核微环境中基因调控机制的组织与组装。
2. 核微环境的组合组装与组织是由支架蛋白在靶基因启动子的多个位点以及亚核结构域中介导的。调控机制在核微环境中的这种局灶性区室化可能调节生理应答性调控网络的动态形成和活性，并提供控制基因激活、抑制或协同调控程度所需的因子阈值浓度。
3. 支架蛋白在细胞核内特定位点的靶向定位支持了它们在生物调控中的参与，并反映了癌症相关改变对基因表达的潜在影响。
4. 实体瘤、白血病和淋巴瘤在核形态以及核内基因、转录本和调控复合物的结构组织方面显示出显著改变。改变的核微环境实例包括白血病中的早幼粒细胞白血病（PML）体和急性髓系白血病（AML）灶、某些实体瘤中的核仁以及广泛的染色体重排。
5. 对癌症中经常发生重排的主要核区室进行成像，结合基因组学和蛋白质组学分析，可以提高通过肿瘤高通量基因分析所产生的调控特征的生物学和临床相关性。
6. 对参与基因表达的核机制在时间和空间上的组织方式（这一机制在肿瘤中受损）的机理研究，为诊断和治疗提供了一个新的平台。

英文摘要：

Nucleic acids and regulatory proteins are compartmentalized in microenvironments within the nucleus. This subnuclear organization may support convergence and the integration of physiological signals for the combinatorial control of gene expression, DNA replication and repair. Nuclear organization is modified in many cancers. There are cancer-related changes in the composition, organization and assembly of regulatory complexes at intranuclear sites. Mechanistic insights into the temporal and spatial organization of machinery for gene expression within the nucleus, which is compromised in tumours, provide a novel platform for diagnosis and therapy.

摘要翻译： 

核酸和调控蛋白被区隔在细胞核内的微环境中。这种亚核结构可能有助于生理信号的汇聚与整合，实现对基因表达、DNA复制与修复的组合式调控。在多种癌症中，核内结构发生改变，调控复合物在核内位点的组成、组织与装配均出现与肿瘤相关的变化。对肿瘤中受损的核内基因表达机制在时间与空间上的组织方式进行深入机制研究，为诊断和治疗提供了新的平台。

原文链接：

Nuclear microenvironments in biological control and cancer