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Cellular genes induced by HTLV-1 in CD4+ T cells

CD4 T 细胞中 HTLV-1 诱导的细胞基因

基本信息

批准号：
07670533
负责人：
HASEGAWA Hitoshi
金额：
$ 1.41万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670533/
关键词：
HTLV-I CD4^+ T cells Transmembrane 4 superfamily bZIP Transcription factor Calrefiwlin CD4^+ T cells Calreticulin CD4 T cells Transmembrane 4 Superfamily Leucine zipper leucine zipper Annexin

项目摘要

To examine the changes in CD4^+ T cells after HTLV-I infection, we have performed differential hybridization of a cDNA library, using probes obtained from an ATL cell line as well as probes obtained from normal CD4^+ T cells and the Molt-4 cell line. By differential screening of this library, thirty clones were isolated. These genes were as follows : 6 membranous proteins, 5 oncogenes, 7 cytokines, 2 transcription factors, 6 cellular proteins and 4 unknown genes.Of these genes, SFA-1 (CD151) was a novel member of transmembrane 4 superfamily. The mRNA of the SFA-1 gene is approximately 1.6 kb in size and encodes a protein of 253 amino acids. Expression of SFA-1 gene was either absent or present at a low level in lymphoid cells but was up-regulated after HTLV-I transformation and transactivated by Tax. SFA-1 was broadly expressed in many human cell types and conserved in mouse. Next, we have analyzed the adhesion molecules associated with, and the biological function of SFA-1/PETA-3 (CD151) in HTLV-I-infected T cells and in freshly isolated ATL cells using anti-SFA-1 (CD151) monoclonal antibody. The CD151 molecule was associated with the alpha5beta1 integrin molecule and it enhanced alpha5beta1 integrin-mediated adhesion to fibronectin. In addition, the expression levels of CD151, alpha4beta1 integrin and alpha5beta1 integrin on ATL cells from lymph nodes of lymphoma-type ATL patients were significantly higher than those on circulating ATL cells from leukemia-type ATL patients.SFA-2 is a novel bZIP transcription factor. The mRNA of the SFA-2 gene is approximately 0.9 kb in size and encodes a protein of 125 amino acids, containing a basic region-leucine zipper DNA-binding domain. The SFA-2 gene was strongly expressed in mature T and B lymphocytes, and was up-regulated after transformation of HTLV-I.The SFA-2 did not homodimerize efficiently but formed heterodimer preferentially with c-Jun. The SFA-2/c-Jun heterodimer bound preferentially to the AP-1 and CRE sites.

为了检测HTLV-I感染后CD 4 ^+ T细胞的变化，我们使用从ATL细胞系获得的探针以及从正常CD 4 ^+ T细胞和Molt-4细胞系获得的探针对cDNA文库进行了差异杂交。通过对文库的差异筛选，共获得30个克隆。这些基因包括6个膜蛋白、5个癌基因、7个细胞因子、2个转录因子、6个细胞蛋白和4个未知基因，其中SFA-1（CD 151）是跨膜蛋白4超家族的新成员。SFA-1基因的mRNA大小约为1.6 kb，编码253个氨基酸的蛋白质。SFA-1基因在淋巴样细胞中的表达是不存在的或以低水平存在，但在HTLV-I转化后上调，并被Tax反式激活。SFA-1广泛表达于多种人类细胞类型中，在小鼠中是保守的。接下来，我们使用抗SFA-1（CD 151）单克隆抗体分析了与SFA-1/PETA-3（CD 151）相关的粘附分子以及HTLV-1感染的T细胞和新鲜分离的ATL细胞中SFA-1/PETA-3（CD 151）的生物学功能。CD 151分子与α 5 β 1整联蛋白分子相关，并增强α 5 β 1整联蛋白介导的与纤连蛋白的粘附。另外，淋巴瘤型ATL患者淋巴结ATL细胞上的CD 151、α 4 β 1整合素和α 5 β 1整合素的表达水平显著高于白血病型ATL患者循环ATL细胞上的表达水平。SFA-2基因的mRNA大小约为0.9 kb，编码125个氨基酸的蛋白质，含有碱性区域-亮氨酸拉链DNA结合结构域。SFA-2基因在成熟的T和B淋巴细胞中有强表达，转化HTLV-Ⅰ后表达上调，SFA-2不能有效地同二聚化，但与c-Jun形成异二聚体，SFA-2/c-Jun异二聚体优先结合AP-1和CRE位点。