Maul G G
Wistar Institute, Philadelphia, PA 19104, USA.
Bioessays. 1998 Aug;20(8):660-7. doi: 10.1002/(SICI)1521-1878(199808)20:8<660::AID-BIES9>3.0.CO;2-M.
Within the highly organized nuclear structure, specific nuclear domains (ND10) are defined by accumulations of proteins that can be interferon-upregulated, implicating ND10 as sites of a nuclear defense mechanism. Compatible with such a mechanism is the deposition of herpesvirus, adenovirus, and papovavirus genomes at the periphery of ND10. However, these DNA viruses begin their transcription at ND10 and consequently initiate replication at these sites, suggesting that viruses have evolved ways to circumvent this potential cellular defense and exploit it. Other ND10-associated proteins belong to ubiquitin-related pathways. These findings, together with the accumulation of various overexpressed cellular and viral proteins, suggest that ND10 function as nuclear dumps or as nuclear depots. Consistent with the recruitment or deposition of various proteins and viral genomes adjacent to ND10, ND10 themselves may only be protein accumulations at specific but as yet undefined nuclear deposition sites. The concept of specific nuclear deposition sites may explain the juxtaposition of various nuclear bodies and allows testable predictions about a potential supramolecular regulatory mechanism whereby proteins are selectively segregated or released by global changes induced in nuclear functions such as viral infections, stress, or hormonal induction.
在高度有序的核结构中,特定的核结构域(ND10)由可被干扰素上调的蛋白质聚集所定义,这表明ND10是核防御机制的位点。疱疹病毒、腺病毒和乳头瘤病毒基因组在ND10周边的沉积与这种机制相符。然而,这些DNA病毒在ND10处开始转录,并因此在这些位点启动复制,这表明病毒已经进化出规避这种潜在细胞防御并加以利用的方式。其他与ND10相关的蛋白质属于泛素相关途径。这些发现,连同各种过表达的细胞和病毒蛋白质的积累,表明ND10起到核垃圾场或核仓库的作用。与各种蛋白质和病毒基因组在ND10附近的募集或沉积一致,ND10本身可能只是特定但尚未明确的核沉积位点处的蛋白质聚集物。特定核沉积位点的概念可以解释各种核体的并列,并允许对一种潜在的超分子调节机制进行可验证的预测,即通过病毒感染、应激或激素诱导等核功能的全局变化来选择性地分离或释放蛋白质。