Late mitotic failure in mice lacking Sak, a polo-like kinase
| Autor: | Pam Cheung, J.C. Macmillan, Anna Kozarova, Carol J. Swallow, James C. Cross, John W. Hudson, James W. Dennis |
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| Rok vydání: | 2001 |
| Předmět: |
Ubiquitin-Protein Ligases
Molecular Sequence Data Mitosis Polo-like kinase Cyclin B Protein Serine-Threonine Kinases Biology Anaphase-Promoting Complex-Cyclosome General Biochemistry Genetics and Molecular Biology Histones Ligases Mice 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins Humans Cleavage furrow Amino Acid Sequence Cyclin B1 Phosphorylation Telophase 030304 developmental biology Anaphase Mice Knockout 0303 health sciences Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Ubiquitin-Protein Ligase Complexes Life Sciences 3T3 Cells Molecular biology Cell biology 030220 oncology & carcinogenesis biological phenomena cell phenomena and immunity General Agricultural and Biological Sciences Multipolar spindles Cytokinesis |
| Zdroj: | Biological Sciences Publications |
| ISSN: | 0960-9822 |
| Popis: | Polo-like kinases in yeast, flies, and mammals regulate key events in mitosis. Such events include spindle formation at G2/M, the anaphase-promoting complex (APC) at the exit from mitosis, the cleavage structure at cytokinesis, and DNA damage checkpoints in G2/M. Polo-like kinases are distinguished by two C-terminal polo box (pb) motifs, which localize the enzymes to mitotic structures. We previously identified Sak, a novel polo-like kinase found in Drosophila and mammals. Here, we demonstrate that the Sak kinase has a functional pb domain that localizes the enzyme to the nucleolus during G2, to the centrosomes in G2/M, and to the cleavage furrow during cytokinesis. To study the role of Sak in embryo development, we generated a Sak null allele, the first polo-like kinase to be mutated in mice. Sak −/− embryos arrested after gastrulation at E7.5, with a marked increase in mitotic and apoptotic cells. Sak −/− embryos displayed cells in late anaphase or telophase that continued to express cyclin B1 and phosphorylated histone H3. Our results suggest that Sak is required for the APC-dependent destruction of cyclin B1 and for exit from mitosis in the postgastrulation embryo. |
| Databáze: | OpenAIRE |
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