Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 7; no. 11; pp. 1173 - 1182
• Main Authors: Marumoto, Tomotoshi, Hirota, Toru, Morisaki, Tetsuro, Kunitoku, Naoko, Zhang, Dongwei, Ichikawa, Yasuko, Sasayama, Takashi, Kuninaka, Shinji, Mimori, Tatsuyuki, Tamaki, Norihiko, Kimura, Masashi, Okano, Yukio, Saya, Hideyuki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2002
• Subjects: Animals; Antibodies - immunology; Aurora Kinase A; Aurora Kinases; Cell Cycle Proteins; Cyclin B1; Cyclin-Dependent Kinases - physiology; Enzyme Activation - physiology; G2 Phase - physiology; HeLa Cells; Humans; Mitosis - physiology; Phosphorylation; Protein Kinases - immunology; Protein Kinases - physiology; Protein-Serine-Threonine Kinases; Rats; Xenopus Proteins
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1046/j.1365-2443.2002.00592.x

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.