Angel P, Hattori K, Smeal T, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093.
Cell. 1988 Dec 2;55(5):875-85. doi: 10.1016/0092-8674(88)90143-2.
Binding of the human transcription factor Jun/AP-1 to a conserved 8 bp nucleotide sequence (TRE) is responsible for increased transcription of different cellular genes in response to tumor promoters, such as TPA, and serum factors. Enhanced Jun/AP-1 activity in TPA-stimulated cells is regulated by two different mechanisms: a posttranslational event acting on pre-existing Jun/AP-1 molecules, and transcriptional activation of jun gene expression leading to an increase in the total amount of Jun/AP-1. Induction of jun transcription in response to TPA is mediated by binding of Jun/AP-1 to a high-affinity AP-1 binding site in the jun promoter region. Site-specific mutagenesis of this binding site prevents TPA induction and trans-activation by Jun/AP-1. These results clearly demonstrate that jun transcription is directly stimulated by its own gene product. This positive regulatory loop is likely to be responsible for prolonging the transient signals generated by activation of protein kinase C.
人类转录因子Jun/AP-1与保守的8个碱基对核苷酸序列（TRE）的结合，负责响应肿瘤启动子（如佛波酯）和血清因子时不同细胞基因转录的增加。佛波酯刺激细胞中增强的Jun/AP-1活性受两种不同机制调节：一种是作用于预先存在的Jun/AP-1分子的翻译后事件，另一种是jun基因表达的转录激活，导致Jun/AP-1总量增加。响应佛波酯时jun转录的诱导是由Jun/AP-1与jun启动子区域中的高亲和力AP-1结合位点结合介导的。该结合位点的位点特异性诱变可阻止佛波酯诱导和Jun/AP-1的反式激活。这些结果清楚地表明，jun转录直接受其自身基因产物的刺激。这种正调控环可能负责延长蛋白激酶C激活产生的瞬时信号。
