Human T cell leukemia virus type 1 oncoprotein tax targets the human mitotic checkpoint protein MAD1
Human T cell leukemia virus type 1 oncoprotein tax targets the human mitotic checkpoint protein MAD1
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DOI：
10.1016/s0092-8674(00)81148-4
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发表时间：
1998-04-03
期刊：
影响因子：
64.5
通讯作者：
Jeang, KT
中科院分区：
文献类型：
--
作者：
Jin, DY;Spencer, F;Jeang, KT
在寻找HTLV-I癌蛋白税的细胞靶标时，我们确定了TXBP181，我们将其描述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的序列保护，S/G（2）/M相期间的高磷酸化以及用Nocodazole处理细胞后，并与HSMAD2结合。 HSMAD1充当同型二聚体。它位于中期期间的中心体，并在后期和末期期间的纺锤体中区和中体。税收或跨量为阴性TXBP181的表达导致多核细胞，这是一种与HSMAD1功能丧失一致的表型。我们提出了一种病毒转化模型，其中税收目标是TXBP181，从而废除了有丝分裂检查点。
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/G(2)/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.