Isolation of genes encoding NF-kB activator in adult T-cell leukemia

成人 T 细胞白血病中编码 NF-kB 激活剂的基因的分离

• 批准号: 15590998
• 负责人: FUJII Masahiro
• 金额: $ 2.37万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590998/
• 关键词: HTLV-1; NF-kB; ATL; Virus; Tax; Apoptosis; Leukemia; Oncogenesis; 発ガン; 感染; トランスフォメーション

Human T-cell leukemia virus type 1(HTLV-1) is associated with the development of adult T-cell leukemia(ATL). HTLV-1 encoded Taxi oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-kB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-kB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-kB in ATL cells using a retroviral functional cloning strategy. Using enhanced green fluorescent protein(EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-kB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-kB. Elevated expression of CD30 was identified in all ATL and HTLV-1 transformed T-cell lines examined, and primary ATL cells from a small number of patients. Elevated CD30 expression is considered one of the causes of constitutive NF-kB activation in ATL cells, and may be involved in ATL development.

人类T细胞白血病病毒1型（HTLV-1）与成人T细胞白血病（ATL）的发展有关。HTLV-1编码的Taxi癌蛋白通过NF-κ B途径激活参与细胞生长和抗凋亡的基因的转录，并且被认为在ATL的发病机制中起关键作用。虽然Tax 1表达通常在ATL细胞中丢失或最小，但这些细胞仍显示出高组成性NF-kB活性，表明ATL细胞中的遗传或表观遗传变化诱导不依赖于Tax 1的活化。本研究的目的是确定负责的ATL细胞中的NF-κ B的组成性激活的分子，使用逆转录病毒功能性克隆策略。使用增强的绿色荧光蛋白（EGFP）表达和杀稻瘟菌素抗性作为选择标记，从ATL细胞系获得了在Rat-1细胞中表现出组成型NF-κ B活性的几个逆转录病毒cDNA克隆，包括全长CD 30。在组成性激活NF-κ B的Rat-1细胞中外源性稳定表达CD 30。在检查的所有ATL和HTLV-1转化的T细胞系以及来自少数患者的原代ATL细胞中鉴定出CD 30表达升高。升高的CD 30表达被认为是ATL细胞中组成性NF-kB活化的原因之一，并且可能参与ATL的发展。

项目成果

Fukushi M, et al.: "Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with human myeloid cell nuclear differentiation antigen induced by interferon α"Virus Genes. 27(3). 237-247 (2003)

Fukushi M 等人：“卡波西肉瘤相关疱疹病毒的潜伏期相关核抗原与干扰素 α 诱导的人骨髓细胞核分化抗原相互作用”病毒基因 27(3)。

PDZ Domain-Binding Motif of Human T-cell Leukemia Virus Type 1 Tax Oncoprotein Augments the Transforming Activity in a Rat Fibroblast Cell

人类 T 细胞白血病病毒 1 型税癌蛋白的 PDZ 结构域结合基序增强大鼠成纤维细胞的转化活性

• 发表时间: 2004
• 期刊: Virology 318(1)
• 作者: Hirata A;et al.
• 通讯作者: et al.

Mori M.et al.: "Aberrant transcription through NF-kB/Rel and AP-1 in adult T-cell leukemia"Gann Monobraph on Cancer Research. 50. 73-92 (2003)

Mori M.等人：“成人 T 细胞白血病中 NF-kB/Rel 和 AP-1 的异常转录”Gann Monobraph 癌症研究。

Nucleotide sequences and functions of the Epstein-Barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas

从唾液腺淋巴上皮癌中分离出的 Epstein-Barr 病毒潜伏膜蛋白 1 基因的核苷酸序列和功能

• 发表时间: 2005
• 期刊: Virus Genes 30(2)
• 作者: Masahiro Morita;Toru Suzuki;Kentaro Ito;Tadashi Yamamoto;Hall WW;Niinuma A;Tsubata C;Higuchi M;Kawakami H;Jen KY
• 通讯作者: Jen KY

Ohashi M., et al.: "Human T-cell Leukemia Virus Type 1 Tax Oncoprotein Induces and Interacts with a Multi-PDZ Domain Protein, MAGI-3"Virology. (In press). (2004)

Ohashi M. 等人：“人类 T 细胞白血病病毒 1 型税癌蛋白诱导多 PDZ 结构域蛋白 MAGI-3 并与之相互作用”病毒学。