XAF1在IFN-γ诱导细胞凋亡过程中的分子机理研究

X染色体连锁的凋亡抑制蛋白相关因子1（XIAP-associated factor 1，XAF1），是一种抑癌基因，参与调控细胞凋亡的关键蛋白。它可通过XIAP依赖途径及非XIAP依赖途径促进细胞凋亡，但是其详尽的分子机理未知。前期研究发现，IFN-γ能促进病毒感染的细胞发生凋亡而抑制病毒增殖，且XAF1在IFN-γ处理后的细胞及IFN-γ和病毒两者协同作用后显著上调表达，推测XAF1在IFN-γ促进病毒感染细胞凋亡过程中起着重要作用。本研究拟通过比较IFN-γ、STIV及两者协同下对XAF1、XIAP的表达调控，以及通过过表达或者RNA干扰技术，研究XAF1在IFN-γ诱导细胞凋亡中作用，并通过酵母双杂交技术筛选非XIAP依赖途径中与XAF1相互作用蛋白且对功能进行验证，一方面可阐明XAF1对IFN-γ诱导细胞凋亡的作用机理，另一方面可完善XAF1促进细胞凋亡的分子机理。

XIAP-associated factor 1 (XAF1), a tumor repressor, is a key molecular in regulating apoptosis. It can induce apoptosis through XIAP-dependent pathway or XIAP-independent pathway, however the molecular mechanism is not clear. Our previous result showed that IFN-γ could induce STIV-infected cells apoptosis to resist viral replication, and the mRNA expression level of XAF1 was significantly increased after cells treatment with IFN-γ, and especially after infection with STIV, indicating that XAF1 played an important role in apoptosis induced by IFN-γ. In this study, we aim to study the immune regulation of IFN-γ on the expression of XAF1, XIAP etc, the effect of XAF1 in IFN-γ induced apoptosis, and the potential interacting protein of XAF1. It is believed that this proposed research will provide novel insights into the molecular mechanism of XAF1 on cell apoptosis induced by IFN-γ, and will replenish the molecular mechanism of XAF1 induced apoptosis.