title: Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells.
abstract: 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.
authors.affiliation: Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Marumoto
authors.forename: Toru
authors.initials: T
authors.lastname: Hirota
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Morisaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Kunitoku
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuninaka
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Mimori
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tamaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Okano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: 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
chemical_list: 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