THE JUN PROTO-ONCOGENE IS POSITIVELY AUTOREGULATED BY ITS PRODUCT, JUN/AP-1
THE JUN PROTO-ONCOGENE IS POSITIVELY AUTOREGULATED BY ITS PRODUCT, JUN/AP-1
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DOI：
10.1016/0092-8674(88)90143-2
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发表时间：
1988-12-02
期刊：
影响因子：
64.5
通讯作者：
KARIN, M
中科院分区：
文献类型：
--
作者：
ANGEL, P;HATTORI, K;KARIN, M
人转录因子 Jun/AP-1 与保守的 8 bp 核苷酸序列 (TRE) 的结合负责响应肿瘤启动子（例如 TPA）和血清因子来增加不同细胞基因的转录。 TPA 刺激细胞中 Jun/AP-1 活性的增强受到两种不同机制的调节：作用于预先存在的 Jun/AP-1 分子的翻译后事件，以及导致 Jun/AP-1 总量增加的 jun 基因表达的转录激活。 jun/AP-1 与 jun 启动子区域的高亲和力 AP-1 结合位点的结合介导了对 TPA 反应的 jun 转录诱导。该结合位点的位点特异性诱变可防止 Jun/AP-1 的 TPA 诱导和反式激活。这些结果清楚地表明jun转录是由其自身基因产物直接刺激的。这种正向调节环路可能是延长蛋白激酶 C 激活产生的瞬时信号的原因。
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 preexisting 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.