C-JUN INHIBITS TRANSCRIPTIONAL ACTIVATION BY THE INSULIN ENHANCER, AND THE INSULIN CONTROL ELEMENT IS THE TARGET OF CONTROL
C-JUN INHIBITS TRANSCRIPTIONAL ACTIVATION BY THE INSULIN ENHANCER, AND THE INSULIN CONTROL ELEMENT IS THE TARGET OF CONTROL
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DOI：
10.1128/mcb.14.1.655
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发表时间：
1994-01-01
影响因子：
5.3
通讯作者：
STEIN, R
中科院分区：
文献类型：
--
作者：
HENDERSON, E;STEIN, R
胰腺β细胞中胰岛素基因的选择性转录受到其增强子的调节，该增强子位于相对于转录起始位点的核苷酸-340和-91之间。增强子内的主要控制元件之一位于核苷酸-100和-91之间（GCCATCTGCT，称为胰岛素控制元件[ICE]），并受到螺旋-环-螺旋（HLH）家族中正作用和负作用转录因子的调节。此前已有研究表明，c-jun原癌基因可以抑制胰岛素基因转录。我们发现 c-jun 抑制 ICE 刺激的转录。 ICE 介导的转录的抑制是由蛋白质羧基末端区域内的序列介导的。这些 c-jun 序列跨越激活结构域和蛋白质的基本亮氨酸拉链 DNA 结合二聚化区域。 c-jun 的两个区域在 jun 家族的其他成员（junB 和 junD）中都是保守的。这些蛋白质还抑制 ICE 介导的转录。 jun 蛋白似乎不会通过直接与 ICE 结合来抑制胰岛素基因转录。 c-jun 和 junB 还阻断两种骨骼肌特异性 HLH 蛋白 MyoD 和肌细胞生成素的反式激活潜力。这些结果表明jun蛋白可能是骨骼肌和胰腺β细胞中用于调节HLH介导的活性的常见转录控制因子。我们讨论了这些观察结果对胰腺β细胞中胰岛素基因转录的可能意义。
Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. One of the principal control elements within the enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as the insulin control element [ICE]) and is regulated by both positive- and negative-acting transcription factors in the helix-loop-helix (HLH) family. It was previously shown that the c-jun proto-oncogene can repress insulin gene transcription. We have found that c-jun inhibits ICE-stimulated transcription. Inhibition of ICE-directed transcription is mediated by sequences within the carboxy-terminal region of the protein. These c-jun sequences span an activation domain and the basic leucine zipper DNA binding-dimerization region of the protein. Both regions of c-jun are conserved within the other members of the jun family:junB and junD. These proteins also suppress ICE-mediated transcription. The jun proteins do not appear to inhibit insulin gene transcription by binding directly to the ICE. c-jun and junB also block the trans-activation potential of two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results suggests that the jun proteins may be common transcription control factors used in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity. We discuss the possible significance of these observations to insulin gene transcription in pancreatic beta cells.