凋亡是一个重要的生物学过程，许多疾病（例如肿瘤）的发生发展都与凋亡过程的紊乱密切相关。作为细胞中最重要的肿瘤抑制基因，p53是一个高效的凋亡启动因子，它在细胞凋亡过程中的关键调控作用使其成为了肿瘤治疗的重要靶点。因此，进一步阐明p53的促凋亡调控机制将有助于发现肿瘤发生发展中的新分子事件，对肿瘤的治疗起到指导意义。在我们前期对果蝇的研究中，NSE4，SMC5/6复合体的一个成员，作为新的p53相互作用蛋白首次被发现，并且这种相互作用在哺乳动物细胞中也保守存在。通过初步实验我们还发现NSE4缺失会减弱p53的促凋亡作用。因此，本研究拟以果蝇为模式生物，通过体内体外实验，阐明NSE4与p53相互作用的分子机制，探讨该相互作用对p53促凋亡功能的调控作用，综合评价该相互作用的生物学意义，从而完善人们对p53促凋亡机制的理解，为以p53为靶点的肿瘤治疗提供新的理论依据。

Apoptosis, programmed cell death (PCD), is a basic biological phenomenon in multicellular organisms. Many diseases (e.g. cancer ) are associated with apoptosis, which are caused due to dysregulation of apoptotic signalling. As one of the most important tumor suppressor genes, p53 is a paradigm for the central importance of apoptosis checkpoints in the defense against malignant transformation. Inactivation of p53 is an almost universal feature of human cancers. This has spurred a tremendous effort to develop p53 based cancer therapies. In our previous study, we found that Drosophila NSE4, a component of SMC5/6 complex, interacts directly with dp53. This interaction is conserved in mammalian system and it enhances p53 mediated apoptosis. Therefore, in this study, we will choose Drosophila as a model organism to clarify the specific mechanism of the interaction between NSE4 and p53 through in vitro and vivo assays. Based on these data the biological function in apoptosis of this interaction will be evaluated. In summary, this study will provide a novel mechanism of apoptosis, which may fill up the gap in the p53 based cancer therapies.