Late mitotic failure in mice lacking Sak, a polo-like kinase

Curr Biol. 2001 Mar 20;11(6):441-6. doi: 10.1016/s0960-9822(01)00117-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cyclin B / metabolism
  • Cyclin B1
  • Drosophila Proteins*
  • Histones / metabolism
  • Humans
  • Ligases
  • Mice
  • Mice, Knockout
  • Mitosis / physiology*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases

Substances

  • CCNB1 protein, human
  • Ccnb1 protein, mouse
  • CycB protein, Drosophila
  • Cyclin B
  • Cyclin B1
  • Drosophila Proteins
  • Histones
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • PLK4 protein, human
  • Plk4 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Ligases