Hess Jochen, Angel Peter, Schorpp-Kistner Marina
Deutsches Krebsforschungszentrum, Division of Signal Transduction and Growth Control, 69120 Heidelberg, Germany.
J Cell Sci. 2004 Dec 1;117(Pt 25):5965-73. doi: 10.1242/jcs.01589.
The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.
AP-1转录因子主要由Jun、Fos和ATF蛋白二聚体组成。它介导基因调控以响应大量生理和病理刺激,包括细胞因子、生长因子、应激信号、细菌和病毒感染以及致癌刺激。对基因改造小鼠和细胞的研究突出了AP-1在正常发育或导致癌症的肿瘤转化所涉及的各种细胞事件中的关键作用。然而,新出现的证据表明,AP-1对细胞命运决定的贡献关键取决于AP-1亚基的相对丰度、AP-1二聚体的组成、刺激的性质、细胞类型和细胞环境。因此,应在复杂的动态信号通路网络和其他同时响应的核因子的背景下考虑AP-1介导的对增殖、分化、凋亡和转化等过程的调控。