Hai T, Wolfgang C D, Marsee D K, Allen A E, Sivaprasad U
Department of Medical Biochemistry, Ohio State University, Columbus 43210, USA.
Gene Expr. 1999;7(4-6):321-35.
The purpose of this review is to discuss ATF3, a member of the ATF/CREB family of transcription factors, and its roles in stress responses. In the introduction, we briefly describe the ATF/CREB family, which contains more than 10 proteins with the basic region-leucine zipper (bZip) DNA binding domain. We summarize their DNA binding and heterodimer formation with other bZip proteins, and discuss the nomenclature of these proteins. Over the years, identical or homologous cDNA clones have been isolated by different laboratories and given different names. We group these proteins into subgroups according to their amino acid similarity; we also list the alternative names for each member, and clarify some potential confusion in the nomenclature of this family of proteins. We then focus on ATF3 and its potential roles in stress responses. We review the evidence that the mRNA level of ATF3 greatly increases when the cells are exposed to stress signals. In animal experiments, the signals include ischemia, ischemia coupled with reperfusion, wounding, axotomy, toxicity, and seizure; in cultured cells, the signals include serum factors, cytokines, genotoxic agents, cell death-inducing agents, and the adenoviral protein E1A. Despite the overwhelming evidence for its induction by stress signals, not much else is known about ATF3. Preliminary results suggest that the JNK/SAPK pathway is involved in the induction of ATF3 by stress signals; in addition, IL-6 and p53 have been demonstrated to be required for the induction of ATF3 under certain conditions. The consequences of inducing ATF3 during stress responses are not clear. Transient transfection and in vitro transcription assays indicate that ATF3 represses transcription as a homodimer; however, ATF3 can activate transcription when coexpressed with its heterodimeric partners or other proteins. Therefore, it is possible that, when induced during stress responses, ATF3 activates some target genes but represses others, depending on the promoter context and cellular context. Even less is understood about the physiological significance of inducing ATF3. We will discuss our preliminary results and some reports by other investigators in this regard.
本综述的目的是讨论转录因子ATF/CREB家族成员之一的ATF3及其在应激反应中的作用。在引言部分，我们简要描述了ATF/CREB家族，该家族包含10多种具有碱性区域-亮氨酸拉链（bZip）DNA结合结构域的蛋白质。我们总结了它们与其他bZip蛋白的DNA结合及异源二聚体形成情况，并讨论了这些蛋白质的命名法。多年来，不同实验室分离出了相同或同源的cDNA克隆，并赋予了不同的名称。我们根据氨基酸相似性将这些蛋白质分为亚组；我们还列出了每个成员的别名，并澄清了该蛋白质家族命名法中一些潜在的混淆之处。然后，我们聚焦于ATF3及其在应激反应中的潜在作用。我们回顾了相关证据，即当细胞暴露于应激信号时，ATF3的mRNA水平会大幅增加。在动物实验中，这些信号包括缺血、缺血再灌注、创伤、轴突切断、毒性和癫痫发作；在培养细胞中，信号包括血清因子、细胞因子、基因毒性剂、诱导细胞死亡的试剂和腺病毒蛋白E1A。尽管有大量证据表明其可被应激信号诱导，但关于ATF3的其他方面却知之甚少。初步结果表明，JNK/SAPK通路参与了应激信号对ATF3的诱导；此外，已证明在某些条件下，IL-6和p53是诱导ATF3所必需的。应激反应期间诱导ATF3的后果尚不清楚。瞬时转染和体外转录分析表明，ATF3作为同源二聚体时会抑制转录；然而，当与异源二聚体伙伴或其他蛋白质共表达时，ATF3可以激活转录。因此，有可能在应激反应期间被诱导时，ATF3会根据启动子背景和细胞背景激活一些靶基因而抑制另一些靶基因。关于诱导ATF3的生理意义，人们了解得更少。我们将讨论我们的初步结果以及其他研究者在这方面的一些报告。
