Mechanism of PDZ domain protein regulation for HTLV-1 tumorigenesis

HTLV-1是成人t细胞白血病的病原体。HTLV-1编码的蛋白Tax1与多种含有PDZ结构域的蛋白相互作用，导致其功能障碍和被感染T细胞的转化。我们发现MAGI-1是一个新的与Tax1相互作用的含有PDZ结构域的蛋白。在Tax1转化的T细胞和HTLV-1感染的T细胞中，MAGI-1的表达显著降低。MAGI-1的敲低增加了细胞内ROS。相反，MAGI-1的过表达减少了细胞内ROS。这些结果表明，MAGI-1是ROS产生的调节因子，而MAGI-1被Tax1失活和随后的异常ROS产生参与了Tax1介导的肿瘤发生。

HTLV-1 is a causative agent of adult T-cell leukemia. HTLV-1 encoded protein Tax1 interacts with various PDZ domain containing proteins, leading to their dysfunction and transformation of infected T cells. We identified MAGI-1 as a new Tax1 interacting PDZ domain containing protein. MAGI-1 expression was dramatically reduced in Tax1 transformed T cells and HTLV-1 infected T cells. Knockdown of MAGI-1 increased intracellular ROS. Conversely, overexpression of MAGI-1 reduced intracellular ROS. These results suggest that MAGI-1 is a regulator of ROS production and MAGI-1 inactivation by Tax1 and subsequent aberrant ROS production is involved in Tax1 mediated tumorigenesis.