细胞凋亡与NF-κB激活的信号传导研究

Signal Transduction of Apoptosis and NF-κB Activation

细胞凋亡是细胞受基因调控的主动死亡方式,对于生物体的正常发育及生理功能的维持具有重要意义。NF-κB是一类在动物细胞中广泛表达的转录因子,其主要生理功能之一是通过诱导凋亡抑制基因的转录,拮抗细胞凋亡的发生。NF-κB的活化调控是细胞生死抉择过程的关键机制之一。现已证明细胞凋亡及NF-κB活化的异常会导致多种人类疾病。本项目从凋亡的执行机制和调控机制两方面入手,对细胞凋亡的机理进行了研究。建立了基于爪蟾卵细胞提取物的非细胞凋亡诱导体系,并利用这一体系,发现爪蟾细胞凋亡特异核酸酶XAD及其特异性的抑制因子IXAD;首次证明磷酸肌酸和核质素在凋亡过程中的作用。克隆了3个新的凋亡诱导基因。在细胞凋亡的调节机制方面,克隆了7个分别作用于NF-κB活化信号通路不同步骤的新的调节基因,发现5个已知蛋白调节不同NF-κB活化途径的新功能。此外,在国际上较早开展了植物细胞凋亡的研究,首次报道体外培养植物细胞凋亡过程中有细胞色素C的释放。

Apoptcsis is a cellular suicide program that is controlled by a cell＇s gene products. NF-κB is a ubiquitously expressed transcription factor that regulates the expression of an exceptionally large number of genes, including those involved in antiapoptosis effects. Abnormality of apoptosis and NF-κB activation may lead to numerous human diseases. The goal of this project is to investigate the regulatory mechanisms of the signal transduction pathway of apoptosis and NF-κB activation. A cell-free apoptosis inducing system consisting of a mixture of X. laevis egg extracts was developed. By using this system, the research group of Dr. SHU and Prof. ZHAI identified apoptotic nuclease and it＇s inhibitor in X. laevis cells; investigated the effects of Phosphoereatine and Nucleoplasmin in apoptosis process. Seven novel genes regulating NF-κB activation were also cloned, and the new functions of five known genes in NF-κB activation regulation were identified. The authors firstly reported Cytochrome C release and easpase activation during apoptosis in plants.