MULTIPLE CIS-ACTING AND TRANS-ACTING ELEMENTS MEDIATE THE TRANSCRIPTIONAL RESPONSE TO PHORBOL ESTERS
MULTIPLE CIS-ACTING AND TRANS-ACTING ELEMENTS MEDIATE THE TRANSCRIPTIONAL RESPONSE TO PHORBOL ESTERS
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DOI：
10.1038/329648a0
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发表时间：
1987-10-15
期刊：
影响因子：
64.8
通讯作者：
KARIN, M
中科院分区：
文献类型：
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作者：
CHIU, R;IMAGAWA, M;KARIN, M
蛋白激酶C在质膜上产生的信号转导中起重要作用。蛋白激酶C的生理激活剂是二酰甘油1，而促进肿瘤的佛波酯，如12-O-十四酰-佛波醇-14乙酸酯(TPA)，构成了另一组特定的激活剂1，2。已有许多细胞底物被蛋白激酶C磷酸化1，3，但直接控制转录以响应蛋白激酶C激活的蛋白质尚未确定。TPA治疗可诱导多种原癌基因4-7、生长因子基因7、8和编码分泌型蛋白的基因9。此外。TPA增加病毒增强子元件10-13的活性。为了确定介导对TPA转录反应的反式作用因子，我们选择猴病毒40(SV40)增强子14作为模型，因为已知它由多个作用因子19-21识别的几个离散作用元件15-18组成。我们在这里报道，SV40增强子至少包含四个不同的TPA反应元件，它们的活性取决于细胞类型。诱导反应可能涉及至少两个不同的翻译后步骤，这两个步骤调节识别这些元件的蛋白质的活性。
Protein kinase C is important in the transduction of signals generated at the plasma membrane. The physiological activators of protein kinase C are diacylglycerols1, and the tumour-promoting phorbol esters, such as 12-O-tetradecanoyI-phorbol-14 acetate (TPA), constitute another group of specific activators1,2. Many cellular substrates for phosphorylation by protein kinase C have been described1,3, but proteins that directly control transcription in response to protein kinase C activation are yet to be identified. TPA treatment leads to induction of various proto-oncogenes4–7, growth factor genes7,8, and genes encoding secreted proteases9. In addition. TPA increases the activity of viral enhancer elements10–13. To identifytrans-acting factors that mediate the transcriptional response to TPA we chose the simian virus 40 (SV40) enhancer14as a model, because it is known to be composed of several discretecis-acting elements15–18which are recognized by multipletrans-acting factors19–21. We report here that the SV40 enhancer contains at least four different TPA responsive elements whose activity is dependent on cell-type. The induction response is likely to involve at least two distinct post-translational steps which modulate the activity of the proteins that recognize these elements.