Clarification of reguratory mechanism of cell proliferation by HTLV-1.

阐明HTLV-1对细胞增殖的调节机制。

• 批准号: 10470077
• 负责人: SHIMOTOHNO Kunitada
• 金额: $ 7.55万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470077/
• 关键词: human T-cell leukemia virus; suppressor oncogene; p53; p53 gene family; co-activator; immortalization; trans-activation; HTLV-1; Tax; 転写抑制

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent for the development of adult T-cell leukemia (ATL). Tax encoded by HTLV-1 plays important role in immortalization of primary human lymphocytes. This capacity of Tax is conducted by modulation of cellular genes regulated by CREB, NFkB. We previously reported that p53, a suppresser oncogene, is also regulated its transacting function by Tax. Purpose in this work is to clarify molecular mechanism of Tax to suppress p53 trans-acting function. We observed that p53 accumulates in cells expressing Tax. Tax mutant which lacks to bind CBP/p300 failed to suppress p53 trans-acting function, suggested that Tax regulates p53 function through interaction with CBP/p300. From binding analysis of CBP/p300 with p53 or Tax, we concluded that suppressive effect of Tax for p53 function is occurred by competitive association with CBP/p300. Suppressive effect of Tax to p53 family gene products other than p53 was also occurred by the similar mechanism seen in p53.

人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）发展的病原体。由HTLV-1编码的Tax在人原代淋巴细胞永生化中起重要作用。Tax的这种能力是通过调节受CREB，NF κ B调节的细胞基因来进行的。我们以前报道过抑癌基因p53也受Tax的调控。本研究旨在阐明Tax抑制p53反式作用的分子机制。我们观察到p53在表达Tax的细胞中积累。缺失CBP/p300结合的Tax突变体不能抑制p53的反式作用，提示Tax通过与CBP/p300相互作用调节p53的功能。通过CBP/p300与p53或Tax的结合分析，我们认为Tax对p53功能的抑制作用是通过与CBP/p300竞争性结合而发生的。Tax对p53以外的p53家族基因产物也有抑制作用，其机制与p53相似。

项目成果

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Ariumi Y. et al.: "HTLV-1 Tax oncoprotein represses the p53-mediated trans-activation function through coativator CBP sequestration"Oncogene. (in press). (2000)

Ariumi Y. 等人：“HTLV-1 Tax 癌蛋白通过共活化剂 CBP 隔离来抑制 p53 介导的反式激活功能”癌基因。

Ariumi, Y.et al.: "HTLV-1 Tax oncoprotein represses the p53-mediated transactivation function through coactivator CBP sequestration"Oncogene. (in press). (2000)

Ariumi, Y. 等人：“HTLV-1 Tax 癌蛋白通过共激活剂 CBP 隔离来抑制 p53 介导的反式激活功能”癌基因。

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