Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
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.
Seki
Akiko
A
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Coppinger
Judith A
JA
Jang
Chang-Young
CY
Yates
John R
JR
Fang
Guowei
G
D000818:Animals; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D025461:Feedback, Physiological; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1; C528235:bora protein, human; C101085:Plk1 protein, Xenopus