Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells.
BACKGROUND
Various mitotic events are controlled by Cdc2-cyclin B and other mitotic kinases. Aurora/Ipl1-related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora-A is a mammalian counterpart of aurora/Ipl1-related kinases and is thought to be a potential oncogene. However, the regulation of aurora-A activation and the commitment of aurora-A in the progression of G2-M phase are largely unknown in mammalian cells.


RESULTS
We demonstrated that aurora-A is activated depending on the activation of Cdc2-cyclin B in mammalian cells. Since Cdc2-cyclin B does not directly phosphorylate aurora-A, indirect pathways such as the inhibition of PP1 by Cdc2-cyclin B may act for the activation of aurora-A kinase. Microinjection of anti-aurora-A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora-A activation at G2-M transition was inhibited by DNA damage, and the over-expression of aurora-A induced the abrogation of the DNA damage-induced G2 checkpoint.


CONCLUSIONS
Aurora-A is activated downstream of Cdc2-cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. Dysregulation of aurora-A induces abnormal G2-M transition in mammalian cells and may lead to chromosome instability, which results in the development and progression of malignant tumours.
Marumoto
Tomotoshi
T
Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Hirota
Toru
T
Morisaki
Tetsuro
T
Kunitoku
Naoko
N
Zhang
Dongwei
D
Ichikawa
Yasuko
Y
Sasayama
Takashi
T
Kuninaka
Shinji
S
Mimori
Tatsuyuki
T
Tamaki
Norihiko
N
Kimura
Masashi
M
Okano
Yukio
Y
Saya
Hideyuki
H
D000818:Animals; D000906:Antibodies / Q000276:immunology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D016195:G2 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000276:immunology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D029867:Xenopus Proteins
D000906:Antibodies; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; C576920:Aurka protein, rat; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases