A Role for PML3 in Centrosome Duplication and Genome Stability

Autor: Kun Sang Chang, Zhi-Xiang Xu, Wen Xin Zou, Pei Lin
Rok vydání: 2005
Předmět:
Cytoplasm
Time Factors
Mitosis
Centrosome cycle
Cell Cycle Proteins
Spindle Apparatus
Promyelocytic Leukemia Protein
Protein Serine-Threonine Kinases
Xenopus Proteins
Cell Line
03 medical and health sciences
Promyelocytic leukemia protein
0302 clinical medicine
Aurora Kinases
Bone Marrow
Cell Line
Tumor
CDC2-CDC28 Kinases
Humans
Immunoprecipitation
Protein Isoforms
Centrosome duplication
Kinase activity
RNA
Small Interfering
Molecular Biology
030304 developmental biology
Cyclin
Cell Proliferation
Cell Nucleus
Centrosome
0303 health sciences
Genome
biology
Tumor Suppressor Proteins
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 2
Nuclear Proteins
U937 Cells
Cell Biology
Cell biology
Spindle apparatus
Neoplasm Proteins
030220 oncology & carcinogenesis
biology.protein
Protein Kinases
Plasmids
Subcellular Fractions
Transcription Factors
Zdroj: Molecular Cell. 17(5):721-732
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2005.02.014
Popis: 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.
Databáze: OpenAIRE
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