Genetic depletion of Polo-like kinase 1 leads to embryonic lethality due to mitotic aberrancies.
Bioessays
; 38 Suppl 1: S96-S106, 2016 07.
Article
in En
| MEDLINE
| ID: mdl-27417127
ABSTRACT
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays multiple and essential roles during the cell division cycle. Its inhibition in cultured cells leads to severe mitotic aberrancies and cell death. Whereas previous reports suggested that Plk1 depletion in mice leads to a non-mitotic arrest in early embryos, we show here that the bi-allelic Plk1 depletion in mice certainly results in embryonic lethality due to extensive mitotic aberrations at the morula stage, including multi- and mono-polar spindles, impaired chromosome segregation and cytokinesis failure. In addition, the conditional depletion of Plk1 during mid-gestation leads also to severe mitotic aberrancies. Our data also confirms that Plk1 is completely dispensable for mitotic entry in vivo. On the other hand, Plk1 haploinsufficient mice are viable, and Plk1-heterozygous fibroblasts do not harbor any cell cycle alterations. Plk1 is overexpressed in many human tumors, suggesting a therapeutic benefit of inhibiting Plk1, and specific small-molecule inhibitors for this kinase are now being evaluated in clinical trials. Therefore, the different Plk1 mouse models here presented are a valuable tool to reexamine the relevance of the mitotic kinase Plk1 during mammalian development and animal physiology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins
/
Protein Serine-Threonine Kinases
/
Cell Cycle Proteins
/
Chromosome Segregation
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Cytokinesis
/
Mitosis
/
Spindle Apparatus
Limits:
Animals
Language:
En
Journal:
Bioessays
Journal subject:
BIOLOGIA
/
BIOLOGIA MOLECULAR
Year:
2016
Type:
Article
Affiliation country:
Spain