凋亡蛋白酶活化因子1诱导细胞凋亡及相关的抗肿瘤治疗的研究进展

Apoptotic Protease Activating Factor 1 Inducing Apotosis and Related Anti-tumor Therapy——Review

凋亡蛋白酶活化因子1(apoptotic protease activating factor-1,Apaf-1)是线粒体凋亡途径中的重要因子。Apaf-1导致凋亡体的形成,然后激活caspase-9水解。激活的caspase-9能使caspase的下游信号开放执行细胞程序性死亡。由于Apaf-1在DNA损伤诱导凋亡中起到核心作用,故Apaf-1在抗肿瘤及药物耐药方面具有重要性。Apaf-1基因的失活意味着肿瘤疾病进展和化疗耐药。对Apaf-1的深入研究将有助于新的具有临床应用价值的抗肿瘤药物的研制。本文就Apaf-1的生化结构和功能、信号转导通路及抗肿瘤治疗方面的研究进展作一综述。

Apoptotic protease activating factor-1 （Apaf1） is an essential factor in intrinsic mitochondrial pathway of apoptosis activation. Apafl leads to the formation of apoptosome, which then proteolytically activates caspase-9. The activated caspase-9 opens the downstream signal of caspases to execute programmed cell death. Apaf-1 is important for tumor suppression and drug resistance because it plays a central role in DNA damage-induced apoptosis. Inactivation of the Apaf-1 gene is implicated in disease progression and chemoresistance of some malignancies. Further research on the Apaf-1 will contribute to develop a new type of approach to anti-cancer drugs, which might have good prospect in clinical practice. In this paper, the structure and function of Apaf-1, the mechanism involved in Apaf-1 signaling pathway , and appllication of Apaf-1 in tumor therapy were reviewed.