拮抗凋亡转录因子与肿瘤增殖及凋亡

Che-1 in Tumor Proliferation and Apoptosis

肿瘤是目前临床常见的疾病之一。肿瘤的经典治疗方式主要包括手术切除、放疗和化疗。近年来肿瘤治疗的手段不断发展,但许多进展期的肿瘤仍然未见较有效的治疗方式,因此亟需新的治疗手段。肿瘤细胞的特点是具有无限增殖和抵抗凋亡的能力。因此,鉴定参与肿瘤细胞增殖和凋亡的基因将为肿瘤治疗提供潜在的靶点。拮抗凋亡转录因子(apoptosis-antagonizing transcription factor,AATF),又称Che-1,最早发现能与RNA聚合酶Ⅱ(RNA polymeraseⅡ,polⅡ)的核心亚基hRPB11(human RNA polymeraseⅡ(polⅡ)subunit)和视网膜母细胞瘤易感基因(retinoblastoma susceptibility gene,Rb)相互作用,并抑制Rb的生长抑制功能。现又发现,Che-1能与RNA聚合酶I(RNA polymeraseⅠ,polⅠ)结合,进而促进RNA聚合酶I依赖的转录,影响核糖体合成。在细胞应激下,Che-1的定位、稳定性受到翻译后修饰(post-translational modification,PTM)的调控。在肿瘤细胞应对DNA损伤、凋亡刺激及其他应激时,Che-1通过调控增殖和凋亡相关基因,进而调节肿瘤的发生发展。此外,Che-1的表达存在一个负反馈机制调节。本文拟对Che-1在肿瘤中作用的最新进展作一简要综述。

Tumor is a type of most common diseases in clinical practice.The classical treatments of tumors mainly include surgical resection,radiotherapy and chemotherapy.In recent years,the methods of tumor treatment have been developing continuously,but many advanced tumors still have no particularly effective treatment.New treatments are urgently needed.Sustaining proliferation and resisting cell death are important characteristics of tumor cells.Therefore,the identification of genes involved in the proliferation and apoptosis of tumor cells will provide potential targets for tumor therapy.Apoptosis-antagonizing transcription factor(AATF),is also called Che-1,the earliest discovered to interact with RNA polymeraseⅡand Rb.Moreover,Che-1 restrains the activity of Rb and supports cell growth.It is found that Che-1 also binds to RNA polymerase Ⅰ,thereby promoting RNA polymerase Ⅰ-dependent transcription and affecting ribosome synthesis.Under cellular stress,the localization and stability of Che-1 are regulated by post-translational modification.In response to DNA damage,apoptosis stimulation and other stress,Che-1 regulates the occurrence and development of tumors by regulating genes associated with proliferation and apoptosis.In addition,the expression of Che-1 is regulated by a negative feedback mechanism.In this review,we highlight the advances in the roles of Che-1 in tumor development and progression.