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

Transcriptional Regulation of Selectin-ligand Synthetase (Fucosyltransferase VII) Related to Ability of Metastasis in Cancer Cells

选择素配体合成酶（岩藻糖基转移酶 VII）的转录调控与癌细胞转移能力相关

基本信息

批准号：
13670582
负责人：
HIRAIWA Nozomu
金额：
$ 2.24万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670582/
关键词：
Selectin-ligand fucosyltransferase VII Tax CRE T-box one-hybrid CREB ATF T-bet fucosyltransferrase VII One-hybrid法 F7CAF-1

项目摘要

Fucosyltransferase VII (Fuc-T VII) gene encodes a leukocyte/endothelial cell adhesion molecule -ligand sialyl Lewis X synthetase, the expression of which plays important roles in inflammation and even in metastasis of some cancer cells. We have shown that leukemia cells in patients with adult T-cell leukemia strongly express the sialyl Lewis X, the expression level of which significantly correlates with the degree of extravascular infiltration of the leukemic cells, and that the Fuc-T VII gene is transactivated by the HTLV-1 Tax.We identified the Tax-responsive element (TaxRE) in the promoter of the Fuc-T VII gene, which contains a half-palindromic cAMP-responsive element (CRE). We found that several members of the CREB/ATF family and unidentified factors bind to this TaxRE being much homologous to the Tax-responsive viral CRE in the HTLV-1 long terminal repeat-promoter. In addition to the structural similarity, reporter analysis revealed that the TaxRE also bears functional resemblance to the viral CRE, differing from cellular CREs such as ** the somatostatin gene promoter.To clarify the mechanism of such fransactivation in the TaxRE, we utilized the yeast one-hybrid system to clone cDNAs encoding TaxRE-binding factors involved in this transactivation. Besides members of CREB/ATF family, one cDNA was identified as the human homologue of one of the transcription factor T box family, T-bet, T-bet reportedly plays a critical role in differentiation of T lymphocyte to Th1. However, the exact binding sequence of T-bet and the mechanism of transactivation remain to be studied. We showed that T-bet actually binds to the 5' part of the TaxRE and also associates with Tax in vivo, and that T-bet is involved in the regulation of the Fuc-T VII gene in association with CREB/ATF family and Tax. These results suggest an important role for T-bet in HTLV-1 Tax-mediated Fuc-T VII gene transactivation.

岩藻糖基转移酶VII(Fuc-T VII)基因编码一种白细胞/内皮细胞黏附分子-配体唾液酸化Lewis X合成酶，其表达在某些癌细胞的炎症甚至转移中起重要作用。我们发现成人T细胞白血病患者的白血病细胞强烈表达唾液酸化Lewis X，其表达水平与白血病细胞血管外浸润的程度显著相关，并且Fuc-T VII基因被HTLV-1 Tax1反式激活。我们鉴定了Fuc-T VII基因启动子中的税收反应元件(TaxRE)，该元件包含一个半回文cAMP反应元件(CRE)。我们发现CREB/ATF家族的几个成员和未知因素与这种TaxRE结合，与HTLV-1长末端重复序列启动子中的税收应答病毒Cre有很大的同源性。除了结构上的相似性，记者分析发现TaxRE还具有与病毒Cre相似的功能，不同于**生长抑素基因启动子等细胞Cre。为了阐明TaxRE中这种反式激活的机制，我们利用酵母单杂交系统克隆了编码参与这种反式激活的TaxRE结合因子的cDNA。除了CREB/ATF家族的成员外，还发现了一个与人类转录因子T box家族T-bet同源的基因，据报道，T-bet在T淋巴细胞向Th1分化的过程中起着关键作用。然而，T-bet的确切结合序列和反式激活机制仍有待研究。我们发现T-bet实际上与TaxRE的5‘端结合，并且在体内还与Tax结合，该T-bet参与了CREB/ATF家族和Tax相关的Fuc-T VII基因的调控。这些结果提示T-bet在HTLV-1Tax介导的Fuc-T VII基因反式激活中起重要作用。