| First Author | Swallow CJ | Year | 2005 |
| Journal | Oncogene | Volume | 24 |
| Issue | 2 | Pages | 306-12 |
| PubMed ID | 15640847 | Mgi Jnum | J:95395 |
| Mgi Id | MGI:3525939 | Doi | 10.1038/sj.onc.1208275 |
| Citation | Swallow CJ, et al. (2005) Sak/Plk4 and mitotic fidelity. Oncogene 24(2):306-12 |
| abstractText | Sak/Plk4 differs from other polo-like kinases in having only a single polo box, which assumes a novel dimer fold that localizes to the nucleolus, centrosomes and the cleavage furrow. Sak expression increases gradually in S through M phase, and Sak is destroyed by APC/C dependent proteolysis. Sak-deficient mouse embryos arrest at E7.5 and display an increased incidence of apoptosis and anaphase arrest. Sak(+/-) mice are haploinsufficient for tumor suppression, with spontaneous tumors developing primarily in the liver with advanced age. During liver regeneration following partial hepatectomy, Sak(+/-) hepatocytes display a delay in reaching the first M phase, multipolar spindles, disorganized tissue morphology and loss of acuity for cyclin B1 expression. Similarly, Sak(+/-) MEF cells proliferate slowly, and show a high incidence of centrosome hyper-amplification. We suggest that Sak provides feedback to cell cycle regulators, and thereby precision to the switch-like transitions of centrosome duplication and exit-from-mitosis. Sak binds to p53, and studies are underway to provide a molecular context for the Sak-p53 interaction. Animal models of haploinsufficiency and more comprehensive models of cell cycle regulation should contribute to improvements in cancer risk assessment and novel therapies. |
