权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of the Gene-missile therapy against human malignant gliomas using monocyte as a carrier.

使用单核细胞作为载体开发针对人类恶性胶质瘤的基因导弹疗法。

基本信息

批准号：
09671431
负责人：
TAKESHIMA Hideo
金额：
$ 1.98万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The human monocyte chemoattractant protein-1 receptor designated hCCR2 is an essential co-receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein-1, a member of the family of C-C chemokines that mediate monocyte chemotaxis. To elucidate the molecular mechanisms underlying the transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene ; it was approximately 8 kb in length and consisted of three exons divided by two introns. In the 5'-flanking region, there were the typical mammalian promoter consensus elements, a CAAT box and a TATA box, resulting in a single transcription initiation site. In addition, we found clustered tissue-specific cis-regulatory elements such as GATA consensus sequences, Oct-1 binding sequences, and CAAT/enhancer-binding protein binding sequences. Luciferase assays with various promoter deletions and gel mobility shift assays indicated that three cis-regulatory elements located within the region from -89 to +118 are required for basal activity in THP-1 cells. One element is an octamer sequence 36-bp upstream from the TATA box ; it binds mainly to Oct-1 and is capable of increasing transcriptional activity. The other two elements, which are tandem recognition sites of the CAAT/enhancer-binding protein family, are located in the 5'-untranslated region and account for the transcriptional activation as well as the tissue specificity of hCCR2.

命名为hCCR 2的人单核细胞趋化蛋白-1受体是人免疫缺陷病毒进入细胞中的必需辅助受体，也是单核细胞趋化蛋白-1的受体，单核细胞趋化蛋白-1是介导单核细胞趋化性的C-C趋化因子家族的成员。为了阐明hCCR 2转录调控的分子机制，我们克隆并测序了hCCR 2基因;它的长度约为8 kb，由三个外显子和两个内含子组成。在5 '侧翼区，存在典型的哺乳动物启动子共有元件，CAAT盒和TATA盒，导致单个转录起始位点。此外，我们还发现了成簇的组织特异性顺式调控元件，如加塔共有序列、Oct-1结合序列和CAAT/增强子结合蛋白结合序列。不同启动子缺失的荧光素酶分析和凝胶迁移率变化分析表明，位于-89至+118区域内的三个顺式调节元件是THP-1细胞中基础活性所需的。一个元素是一个八聚体序列36 bp上游的TATA框，它主要结合到Oct-1，是能够增加转录活性。另外两个元件是CAAT/增强子结合蛋白家族的串联识别位点，位于5 '-非翻译区，负责hCCR 2的转录激活以及组织特异性。