Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Aurora Kinases
-
Bone Marrow / metabolism
-
CDC2-CDC28 Kinases / metabolism
-
Cell Cycle Proteins
-
Cell Line
-
Cell Line, Tumor
-
Cell Nucleus / metabolism
-
Cell Proliferation
-
Centrosome / metabolism
-
Centrosome / ultrastructure
-
Cyclin-Dependent Kinase 2
-
Cytoplasm / metabolism
-
Genome*
-
Humans
-
Immunoprecipitation
-
Mitosis
-
Neoplasm Proteins / chemistry
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / physiology*
-
Nuclear Proteins / chemistry
-
Nuclear Proteins / genetics
-
Nuclear Proteins / physiology*
-
Plasmids / metabolism
-
Promyelocytic Leukemia Protein
-
Protein Isoforms
-
Protein Kinases / metabolism
-
Protein Serine-Threonine Kinases
-
RNA, Small Interfering / metabolism
-
Spindle Apparatus
-
Subcellular Fractions / metabolism
-
Time Factors
-
Transcription Factors / chemistry
-
Transcription Factors / genetics
-
Transcription Factors / physiology*
-
Tumor Suppressor Proteins
-
U937 Cells
-
Xenopus Proteins
Substances
-
Cell Cycle Proteins
-
Neoplasm Proteins
-
Nuclear Proteins
-
Promyelocytic Leukemia Protein
-
Protein Isoforms
-
RNA, Small Interfering
-
Transcription Factors
-
Tumor Suppressor Proteins
-
Xenopus Proteins
-
PML protein, human
-
Protein Kinases
-
AURKA protein, Xenopus
-
Aurora Kinases
-
Protein Serine-Threonine Kinases
-
CDC2-CDC28 Kinases
-
CDK2 protein, human
-
Cyclin-Dependent Kinase 2