Abstract
A central question in the study of cell proliferation is, what controls cell-cycle transitions? Although the accumulation of mitotic cyclins drives the transition from the G2 phase to the M phase in embryonic cells, the trigger for mitotic entry in somatic cells remains unknown. We report that the synergistic action of Bora and the kinase Aurora A (Aur-A) controls the G2-M transition. Bora accumulates in the G2 phase and promotes Aur-A-mediated activation of Polo-like kinase 1 (Plk1), leading to the activation of cyclin-dependent kinase 1 and mitotic entry. Mechanistically, Bora interacts with Plk1 and controls the accessibility of its activation loop for phosphorylation and activation by Aur-A. Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Aurora Kinases
-
CDC2 Protein Kinase / metabolism
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / metabolism*
-
Cell Line
-
Enzyme Activation
-
Feedback, Physiological
-
G2 Phase
-
HeLa Cells
-
Humans
-
Kinetics
-
Mitosis*
-
Phosphorylation
-
Polo-Like Kinase 1
-
Protein Binding
-
Protein Serine-Threonine Kinases / chemistry
-
Protein Serine-Threonine Kinases / metabolism*
-
Protein Structure, Tertiary
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins / metabolism*
-
Recombinant Fusion Proteins / metabolism
-
Xenopus
-
Xenopus Proteins / metabolism
Substances
-
Cell Cycle Proteins
-
Proto-Oncogene Proteins
-
Recombinant Fusion Proteins
-
Xenopus Proteins
-
bora protein, human
-
Aurora Kinases
-
Plk1 protein, Xenopus
-
Protein Serine-Threonine Kinases
-
CDC2 Protein Kinase