Jin D Y, Spencer F, Jeang K T
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA.
Cell. 1998 Apr 3;93(1):81-91. doi: 10.1016/s0092-8674(00)81148-4.
In searching for cellular targets of the HTLV-I oncoprotein Tax, we identified TXBP181, which we characterized as the human homolog of yeast mitotic checkpoint MAD1 protein. Evidence supporting TXBP181 as HsMAD1 includes sequence conservation with yeast MAD1, hyperphosphorylation during S/G2/M phases and upon treatment of cells with nocodazole, and binding to HsMAD2. HsMAD1 functions as a homodimer. It localizes to the centrosome during metaphase and to the spindle midzone and the midbody during anaphase and telophase. Expression of either Tax or a transdominant-negative TXBP181 results in multinucleated cells, a phenotype consistent with a loss of HsMAD1 function. We propose a model of viral transformation in which Tax targets TXBP181, thereby abrogating a mitotic checkpoint.
在寻找人嗜T细胞病毒I型（HTLV-I）癌蛋白Tax的细胞靶点过程中，我们鉴定出了TXBP181，其被确定为酵母有丝分裂检查点MAD1蛋白的人类同源物。支持TXBP181作为HsMAD1的证据包括与酵母MAD1的序列保守性、在S/G2/M期以及用诺考达唑处理细胞后发生的过度磷酸化，以及与HsMAD2的结合。HsMAD1作为同源二聚体发挥作用。在中期它定位于中心体，在后期和末期定位于纺锤体中间区和中间体。Tax或显性负性TXBP181的表达都会导致多核细胞的产生，这一表型与HsMAD1功能丧失一致。我们提出了一种病毒转化模型，其中Tax靶向TXBP181，从而废除有丝分裂检查点。
