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

人t细胞白血病病毒1型（HTLV-1）是成人t细胞白血病（ATL）的病原体。HTLV-1编码的Tax在人原代淋巴细胞的永生化中起重要作用。这种能力是通过调节由CREB、NFkB调控的细胞基因来实现的。我们之前报道过p53，一个抑癌基因，也受Tax调控其交易功能。本研究的目的是阐明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。缺乏结合CBP/p300的Tax突变体未能抑制p53的反式作用功能，提示Tax通过与CBP/p300的相互作用调控p53的功能。通过对CBP/p300与p53或Tax的结合分析，我们得出结论，Tax对p53功能的抑制作用是通过与CBP/p300的竞争性结合而发生的。tax3对p53家族基因产物的抑制作用也与p53相似。

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.