Vlahopoulos Spiros A, Logotheti Stella, Mikas Dimitris, Giarika Athina, Gorgoulis Vassilis, Zoumpourlis Vassilis
Unit of Biomedical Applications, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Bioessays. 2008 Apr;30(4):314-27. doi: 10.1002/bies.20734.
Activating Transcription Factor-2 is a sequence-specific DNA-binding protein that belongs to the bZIP family of proteins and plays diverse roles in the mammalian cells. In response to stress stimuli, it activates a variety of gene targets including cyclin A, cyclin D and c-jun, which are involved in oncogenesis in various tissue types. ATF-2 expression has been correlated with maintenance of a cancer cell phenotype. However, other studies demonstrate an antiproliferative or apoptotic role for ATF-2. In this review, we summarize the signaling pathways that activate ATF-2, as well as its downstream targets. We examine the role of ATF-2 in carcinogenesis with respect to other bZIP proteins, using data from studies in human cancer cell lines, human tumours and mouse models, and we propose a potential model for its function in carcinogenesis, as well as a theoretical basis for its utility in anticancer drug design.
活化转录因子2是一种序列特异性DNA结合蛋白,属于bZIP蛋白家族,在哺乳动物细胞中发挥多种作用。在应激刺激下,它会激活多种基因靶点,包括细胞周期蛋白A、细胞周期蛋白D和c-jun,这些靶点参与了各种组织类型的肿瘤发生。ATF-2的表达与癌细胞表型的维持相关。然而,其他研究表明ATF-2具有抗增殖或凋亡作用。在这篇综述中,我们总结了激活ATF-2的信号通路及其下游靶点。我们利用来自人类癌细胞系、人类肿瘤和小鼠模型研究的数据,研究了ATF-2相对于其他bZIP蛋白在致癌作用中的作用,并提出了其在致癌作用中的潜在功能模型,以及其在抗癌药物设计中应用的理论基础。