PML核体是一种由PML蛋白相互作用为基础的亚细胞核结构，具有肿瘤抑制及病毒防御等多种生物学功能。PML核体的正常形成是其发挥功能的关键，而目前对其形成机制的认识还有待完善。PML蛋白至少存在6种定位于细胞核中的亚型，这些核亚型具有相同的N端和不同的C端。以往有关PML核体形成机制的研究大多集中在PML蛋白N端结构域的上，而对PML各亚型C端在核体形成中的作用认识很少。我们的前期研究表明PML亚型I、II和V的C端区域在核体形成、运动速率以及定位方面也起了一定的作用。在本课题中，我们将深入研究这三个亚型在核体形成中的具体作用和机制，研究内容包括：1）研究PML亚型I和II对PML核体形成及超微结构的影响及机制；2）研究PML-I和-II在PML核体定位中的作用及机制；3）研究PML-V对PML核体稳定性及功能的影响。该项目的研究结果将为全面揭示PML核体的形成机制及功能调控提供理论基础。

PML nuclear bodies (PML-NBs) are a type of sub-nuclear structures assembled through PML protein mediated self-interaction. These structures are implicated in a wide range of important functions, notably tumor suppression and viral defense. Normal assembly of PML-NBs is of great importance in execution of their functions; however, the detailed molecular mechanisms have not been fully uncovered. The PML protein has a least 6 nuclear splice isoforms, which share a common N-terminal region but differ in their C-termini. Previous studies on PML-NB formation have mostly focused the N-terminal region of PML and the role of the C-termini of PML isoforms in this process has not been explored. Our previous studies have shown that the C-termini of PML-I,-II and -V may play important roles in the assembly, mobility and localization of PML-NBs. In this proposal, we plan to investigate the exact role of these isoforms and their mechanisms of actions. Specifically, we will examine 1) whether PML-I and -II contribute to the normal structure of PML-NB; 2) whether PML-I and -II mediate the localization of PML-NBs and 3) whether PML-V regulates the stability and functions of PML-NBs. We believe the results of this proposal will greatly improve the understanding of the regulation and assembly of PML-NBs.