Incomplete cytokinesis and induction of apoptosis by overexpression of the mammalian polo-like kinase, Plk3.
The polo-like kinases (Plks) are a family of conserved serine/threonine kinases that play a critical role in the normal progression of cells through mitosis. The Plk3 serine/threonine kinase is a mammalian member of this family. Overexpression of Plk3 in mammalian cells suppresses proliferation and inhibits colony formation. Subsequent analysis demonstrated that overexpression of Plk3 induces chromatin condensation and apoptosis. This phenotype could not be inhibited by coexpression of Bcl-2 and was partially dependent on the COOH-terminal domain of Plk3 but not on the catalytic activity of Plk3. Analysis of EGFP-Plk3 subcellular localization revealed that Plk3 localizes to the cellular cortex and to the cell midbody during exit from mitosis and is consistent with a role in cytokinesis. These data suggest that overexpression or ectopic suppression of Plk3 interferes with cellular proliferation by impeding cytokinesis.
Conn
C W
CW
Departments of Cell Biology, University of Cincinnati College of Medicine, Ohio 45267-0521, USA.
Hennigan
R F
RF
Dai
W
W
Sanchez
Y
Y
Stambrook
P J
PJ
D000483:Alleles; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins; D000097868:Polo-like Kinases
D017304:Annexin A5; D018797:Cell Cycle Proteins; D002843:Chromatin; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D017346:Protein Serine-Threonine Kinases; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011691:Puromycin; D025521:Tumor Suppressor Proteins; C486256:PLK3 protein, human; D000097868:Polo-like Kinases