• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic β-cells
【24h】

Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic β-cells

机译：MAPK信号传导对胰腺β细胞CHOP-10 / GADD153基因表达的差异调节

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

CHOP-10 (GADD153/DDIT-3) is a bZIP protein involved in differentiation and apoptosis. Its expression is induced in response to stresses such as nutrient deprivation, perturbation of the endo-plasmic reticulum, redox imbalance, and UV exposure. Here we show that CHOP expression is induced in cultured pancreatic β-cells maintained in a basal glucose concentration of 5.5 mM and repressed by stimulatory glucose (≥ 11 mM). Both induction and repression of CHOP are dependent on the MAPKs ERK1 and ERK2. Two regulatory composite sites containing overlapping MafA response elements (MARE) and CAAT enhancer binding (CEB) elements regulate transcription in an ERK1/2-dependent manner. One site (MARE-CEB), from -320 to -300 bp in the promoter, represses transcription. The other site (CEB-MARE), from +2,628 to +2,641 bp in the first intron of the CHOP gene, activates it. MafA can influence transcription of both sites. The MARE-CEB is repressed by MafA, whereas the CEB-MARE site, which is homologous to the A2C1 component of the glucose-sensitive RIPE3b region of the insulin gene promoter, is activated by MafA. These results indicate that ERK1/2 have dual roles in regulating CHOP gene expression via both promoter and intronic regions, depending on environmental and metabolic stresses imposed on pancreatic β-cells.
机译：CHOP-10（GADD153 / DDIT-3）是一种bZIP蛋白，参与分化和凋亡。它的表达是响应诸如营养缺乏，内质网微扰，氧化还原失衡和紫外线照射等压力而诱导的。在这里，我们显示CHOP表达是在维持在5.5 mM的基础葡萄糖浓度并被刺激性葡萄糖（≥11 mM）抑制的培养的胰腺β细胞中诱导表达的。 CHOP的诱导和抑制均取决于MAPK ERK1和ERK2。包含重叠的MafA反应元件（MARE）和CAAT增强子结合（CEB）元件的两个调节性复合位点以ERK1 / 2依赖性方式调节转录。启动子中从-320到-300 bp的一个位点（MARE-CEB）抑制转录。 CHOP基因的第一个内含子中从+2,628到+2,641 bp的另一个位点（CEB-MARE）将其激活。 MafA可以影响两个位点的转录。 MafA抑制MARE-CEB，而MafA激活与胰岛素基因启动子的葡萄糖敏感RIPE3b区的A2C1组分同源的CEB-MARE位点。这些结果表明，ERK1 / 2在通过启动子和内含子区域调节CHOP基因表达中具有双重作用，这取决于施加于胰腺β细胞的环境和代谢压力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号