A role for PML3 in centrosome duplication and genome stability.
A role for PML3 in centrosome duplication and genome stability.
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DOI：
10.1016/j.molcel.2005.02.014
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发表时间：
2005-03
期刊：
影响因子：
16
通讯作者：
Zhi-xiang Xu;Wen-Xin Zou;P. Lin;K. Chang
中科院分区：
文献类型：
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作者：
Zhi-xiang Xu;Wen-Xin Zou;P. Lin;K. Chang
急性早幼粒细胞白血病(APL)染色体t(15；17)易位干扰的早幼粒细胞白血病基因(PML)编码一种多功能蛋白，参与多种重要的细胞功能。在这里，我们证明了PML定位于中心体，并且PML缺陷会导致中心体扩增。通过使用PML亚型特异性抗体，我们发现PML3特异性与有丝分裂纺锤体的中心体和极点有关。PML3缺乏导致中心体复制检查点的失调。此外，PML3与Aurora A在物理上相互作用，并调节其激酶活性。PML3的特异性敲除可激活CDK2/细胞周期蛋白激酶活性。这项研究的结果表明，PML3通过抑制Aurora A的激活来防止中心体重复，从而在控制中心体复制中发挥直接作用。
The promyelocytic leukemia gene (PML), which is disrupted by the chromosomal translocation t(15;17) in acute promyelocytic leukemia (APL), encodes a multifunctional protein involved in several important cellular functions. Herein, we demonstrate that PML is localized to centrosomes and that PML deficiency leads to centrosome amplification. By using PML isoform-specific antibodies, we found PML3-specific association with the centrosome and the pole of the mitotic spindle. PML3 deficiency leads to dysregulation of the centrosome duplication checkpoint. Furthermore, PML3 physically interacts with Aurora A and regulates its kinase activity. Specific knockdown of PML3 activates Cdk2/cyclin kinase activity. The results of this study implicate a direct role for PML3 in the control of centrosome duplication through suppression of Aurora A activation to prevent centrosome reduplication.