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Late mitotic failure in mice lacking Sak, a polo-like kinase
J W Hudson1, A Kozarova, P Cheung
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5, Ontario, Canada.
Current Biology : CB
|April 13, 2001
Summary
Sak kinase is crucial for cell division regulation in mammals. Its absence in mice leads to mitotic arrest and increased cell death, highlighting its role in embryonic development.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Polo-like kinases (PLKs) are essential regulators of mitosis across eukaryotes.
- PLKs contain C-terminal polo box (pb) motifs for localization to mitotic structures.
- Sak is a novel PLK identified in Drosophila and mammals.
Purpose of the Study:
- To investigate the function of Sak kinase in mammalian embryonic development.
- To characterize the localization and role of Sak during mitosis and cytokinesis.
Main Methods:
- Generated a Sak null allele in mice (Sak-/-).
- Analyzed Sak localization using its functional pb domain.
- Examined mitotic progression, cell death, and protein expression in Sak-/- embryos.
Main Results:
- Sak kinase localizes to the nucleolus, centrosomes, and cleavage furrow.
- Sak-/- embryos exhibit developmental arrest at E7.5 with increased mitotic and apoptotic cells.
- Sak-/- embryos show defects in cyclin B1 degradation and exit from mitosis, with persistent cyclin B1 and phosphorylated histone H3.
Conclusions:
- Sak kinase is essential for proper mitotic exit and embryonic development in mice.
- Sak plays a critical role in the anaphase-promoting complex (APC)-dependent destruction of cyclin B1.
- Sak is indispensable for timely progression through mitosis during post-gastrulation development.