A role for PML3 in centrosome duplication and genome stability

作者：Xu ZX; Zou WX; Lin P; Chang KS^*

来源：Molecular Cell, 2005, 17(5): 721-732.

DOI：10.1016/j.molcel.2005.02.014

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 PML-3-specific association with the centrosome and the pole of the mitotic spindle. PML3 deficiency leads to clysregulation 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.

• 出版日期2005-3-4