• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Transactivation of Involucrin, A Marker of Differentiation in Keratinocytes, by Lens Epithelium-Derived Growth Factor (LEDGF).
【24h】

Transactivation of Involucrin, A Marker of Differentiation in Keratinocytes, by Lens Epithelium-Derived Growth Factor (LEDGF).

机译：晶状体上皮衍生生长因子（LEDGF）反转录激活Involucrin（角质形成细胞分化的标志）。

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

Human involucrin (hINV), first appears in the cytosol of keratinocytes and ultimately cross-linked to membrane proteins via transglutaminase and forms a protective barrier as an insoluble envelope beneath the plasma membrane. Although the function and evolution of involucrin is known, the regulation of its gene expression is not well understood. An analysis of the hINV gene sequence, upstream of the transcription start site (-534 to +1 nt) revealed the presence of potential sites for binding of lens epithelium-derived growth factor (LEDGF); stress response element (STRE; A/TGGGGA/T) and heat shock element (HSE; nGAAn). We reported earlier that LEDGF activates stress-associated genes by binding to these elements and elevates cellular resistance to various stresses. Here, gel-shift and super-shift assays confirm the binding of LEDGF to the DNA fragments containing HSEs and STREs that are present in the involucrin gene promoter. Furthermore, hINV promoter linked to CAT reporter gene, cotransfected in human corneal simian virus 40-transformed keratinocytes (HCK), was transactivated by LEDGF significantly. In contrast, the activity of hINV promoter bearing mutations at the WT1 (containing HSE and STRE), WT2 (containing STRE) and WT3 (containing STRE) binding sites was diminished. In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA and hINV protein are increased by four to five-fold. LEDGF is inducible to oxidants. Cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate production of H(2)O(2), showed higher levels of LEDGF mRNA. Furthermore, our immunohistochemical studies revealed that hINV protein is found in the cytoplasm of HCK cells over-expressing LEDGF, but not detectable in the normal HCK cells or HCK cells transfected with vector. This regulation appears to be physiologically important, as over-expression of HCK with LEDGF increases the expression of the endogenous hINV gene and may provide new insight to understand the molecular mechanism of transcriptional regulation of this gene. LEDGF may play an important role in establishing an important barrier in corneal keratinocytes by maintaining epidermal turn-over rate, and protecting HCKs against stress.
机译：人整合素（hINV）首先出现在角质形成细胞的细胞质中，最后通过转谷氨酰胺酶与膜蛋白交联，并形成保护性屏障，成为质膜下的不溶性包膜。尽管整合素的功能和进化是已知的，但对其基因表达的调节却知之甚少。在转录起始位点（-534至+1 nt）上游对hINV基因序列进行分析，发现存在潜在的结合晶状体上皮来源的生长因子（LEDGF）的位点。应力响应元件（STRE; A / TGGGGA / T）和热冲击元件（HSE; nGAAn）。我们之前报道过，LEDGF通过与这些元素结合来激活与压力相关的基因，并提高了细胞对各种压力的抵抗力。在这里，凝胶迁移和超迁移测定法证实了LEDGF与DNA片段的结合，该DNA片段包含在囊蛋白基因启动子中，含有HSE和STRE。此外，与CAT报告基因连接的hINV启动子在人角膜猿猴病毒40转化的角质形成细胞（HCK）中共转染，被LEDGF显着激活。相反，在WT1（含有HSE和STRE），WT2（含有STRE）和WT3（含有STRE）结合位点处携带突变的hINV启动子的活性降低了。另外，在HCK细胞过表达的LEDGF中，hINV mRNA和hINV蛋白的水平增加了四到五倍。 LEDGF可诱导氧化剂。用已知刺激刺激H（2）O（2）生产的12-O-十四烷酰基-phorbol-13-乙酸盐（TPA）处理的细胞显示更高水平的LEDGF mRNA。此外，我们的免疫组织化学研究表明，hINV蛋白存在于过度表达LEDGF的HCK细胞的细胞质中，但在正常的HCK细胞或转染了载体的HCK细胞中却无法检测到。这种调节在生理上似乎很重要，因为用LEDGF过度表达HCK会增加内源性hINV基因的表达，并可能为了解该基因的转录调节分子机制提供新的见解。 LEDGF可能通过维持表皮周转率并保护HCK免受压力而在角膜角质形成细胞中建立重要屏障方面发挥重要作用。

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