Disease relevance of Plk4

• The incidence of spontaneous liver and lung cancers was approximately 15 times high in elderly Plk4+/- mice than in Plk4+/+ littermates [1].
• Loss of heterozygosity occurs frequently (approximately 60%) at polymorphic markers adjacent to the PLK4 locus in human hepatoma [1].

High impact information on Plk4

• The polo-like kinase Plk4 (also called Sak) is required for late mitotic progression, cell survival and postgastrulation embryonic development [1].
• These defects were associated with progressive cell cycle delays, increased spindle irregularities and accelerated hepatocellular carcinogenesis in Plk4+/- mice [1].
• Here we identified a phenotype resulting from Plk4 haploinsufficiency in Plk4 heterozygous cells and mice [1].
• Plk4+/- embryonic fibroblasts had increased centrosomal amplification, multipolar spindle formation and aneuploidy compared with wild-type cells [1].
• Reduced Plk4 gene dosage increases the probability of mitotic errors and cancer development [1].

Biological context of Plk4

• Sak, a murine protein-serine/threonine kinase that is related to the Drosophila polo kinase and involved in cell proliferation [2].
• Northern and in situ RNA analyses of Sak gene expression in mouse embryos and adult tissues revealed that expression was associated with mitotic and meiotic cell division [2].
• The pattern of Sak expression and its sequence homology with the polo gene family suggest that the Sak kinase may play a role in cell proliferation [2].
• Sak is expressed primarily at sites where cell division is most active in adult and embryonic tissues (C. Fode, B. Motro, S. Youseli, M. Heffernan, and J. W. Dennis, Proc. Natl. Acad. Sci. USA 91:6388-6392, 1994) [3].
• Sak(-/-) embryos displayed cells in late anaphase or telophase that continued to express cyclin B1 and phosphorylated histone H3 [4].

Anatomical context of Plk4

• 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 [5].
• The Polo kinase Plk4 functions in centriole duplication [6].
• SAK/PLK4 is required for centriole duplication and flagella development [7].

Other interactions of Plk4

• In addition, during embryogenesis, Sak expression was prominent in the respiratory and olfactory mucosa [2].

References