Sears Thomas K, Angelastro James M
Department of Molecular Biosciences, University of California, Davis School of Veterinary Medicine, Davis, 95616 CA, USA.
Oncotarget. 2017 Sep 20;8(48):84595-84609. doi: 10.18632/oncotarget.21102. eCollection 2017 Oct 13.
Activating transcription factor 5 (ATF5) is a cellular prosurvival transcription factor within the basic leucine zipper (bZip) family that is involved in cellular differentiation and promotes cellular adaptation to stress. Recent studies have characterized the oncogenic role of ATF5 in the development of several different types of cancer, notably glioblastoma. Preclinical assessment of a systemically deliverable dominant-negative ATF5 (dnATF5) biologic has found that targeting ATF5 results in tumor regression and tumor growth inhibition of glioblastoma xenografts in mouse models. In this review, we comprehensively and critically detail the current scientific literature on ATF5 in the context of cellular differentiation, survival, and response to stressors in normal tissues. Furthermore, we will discuss how the prosurvival role of ATF5 aides in cancer development, followed by current advances in targeting ATF5 using dominant-negative biologics, and perspectives on future research.
激活转录因子5（ATF5）是碱性亮氨酸拉链（bZip）家族中的一种细胞存活转录因子，参与细胞分化并促进细胞对压力的适应。最近的研究已明确了ATF5在几种不同类型癌症（尤其是胶质母细胞瘤）发生发展中的致癌作用。对一种可全身递送的显性负性ATF5（dnATF5）生物制剂的临床前评估发现，靶向ATF5可导致小鼠模型中胶质母细胞瘤异种移植物的肿瘤消退和肿瘤生长抑制。在这篇综述中，我们全面且批判性地详细阐述了当前关于ATF5在正常组织细胞分化、存活及对应激源反应方面的科学文献。此外，我们将讨论ATF5的存活促进作用如何助力癌症发展，接着介绍使用显性负性生物制剂靶向ATF5的当前进展，以及对未来研究的展望。
