The HIV-Tat protein induces chromosome number aberrations by affecting mitosis
The HIV-Tat protein induces chromosome number aberrations by affecting mitosis
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DOI：
10.1002/cm.20070
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发表时间：
2005-07-01
影响因子：
--
通讯作者：
Gigliani, F
中科院分区：
文献类型：
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作者：
Battaglia, PA;Ponti, D;Gigliani, F
为了分析HIV-Tat-微管蛋白相互作用的影响，我们将HIV-Tat纯化蛋白显微注射到果蝇合胞体胚胎中。达特注射后，观察到皮质核周期的时间发生改变;具体而言，核膜破裂和后期启动之间的时间延长，后期启动和下一个核膜的形成之间的时间也延长。这两个时期分别对应于中期的动粒排列和有丝分裂的退出。我们还表明，这两个延迟的后果，特别是损伤诱导达特对着丝粒排列和姐妹染色单体分离的时间在后期。此外，我们表明，达特在果蝇幼虫脑细胞的表达产生了显着比例的多倍体和非整倍体细胞。这里报告的结果表明，达特损害有丝分裂过程和塔特微管蛋白的相互作用似乎是负责观察到的缺陷。多倍体和非整倍体细胞的存在与相当一部分表达达特的细胞的M期延迟或停滞一致，表明有丝分裂纺锤体检查点在达特表达后被覆盖。(c)2005 Wiley-Liss，Inc.
To analyze the effects of the HIV-Tat-tubulin interaction, we microinjected HIV-Tat purified protein into Drosophila syncytial embryos. Following the Tat injection, altered timing of the cortical nuclear cycles was observed; specifically, the period between the nuclear envelope breakdown and anaphase initiation was lengthened as was the period between anaphase initiation and the fort-nation of the next nuclear envelope. These two periods correspond to kinetochore alignment at metaphase and to mitosis exit, respectively. We also demonstrated that these two delays are the consequence of damage specifically induced by Tat on kinetochore alignment and on the timing of sister chromatid segregation at anaphase. Furthermore, we show that the expression of Tat in Drosophila larvae brain cells produces a significant percentage of polyploid and aneuploid cells. The results reported here indicate that Tat impairs the mitotic process and that Tat-tubulin interaction appears to be responsible for the observed defects. The presence of polyploid and aneuploid cells is consistent with a delay or arrest in the M phase of a substantial fraction of the cells expressing Tat, suggesting that mitotic spindle checkpoints are overridden following Tat expression. (c) 2005 Wiley-Liss, Inc.