A role for PML3 in centrosome duplication and genome stability.

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.
Mesh Terms:
Bone Marrow, CDC2-CDC28 Kinases, Cell Cycle Proteins, Cell Line, Cell Line, Tumor, Cell Nucleus, Cell Proliferation, Centrosome, Cyclin-Dependent Kinase 2, Cytoplasm, Genome, Humans, Immunoprecipitation, Mitosis, Mitotic Spindle Apparatus, Neoplasm Proteins, Nuclear Proteins, Plasmids, Protein Isoforms, Protein Kinases, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Subcellular Fractions, Time Factors, Transcription Factors, Tumor Suppressor Proteins, U937 Cells, Xenopus Proteins
Mol. Cell
Date: Mar. 04, 2005
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