title: Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation.
abstract: Aurora-A is involved in chromosome alignment, centrosome maturation, mitotic spindle assembly and regards to an oncogene. Aurora-A is also known to bind to several other proteins affecting its up-regulation or down-regulation and localization. However, how these different binding signals work together to regulate Aurora-A is not properly known. To explore more Aurora-A interacting proteins, the low-copy yeast two-hybrid screening using Aurora-A as bait protein was performed. One novel gene, AIBp, was demonstrated to associate with Aurora-A by the yeast two-hybrid method and in vitro GST pull-down assay. Molecular characterization showed that AIBp possessed a binding site at the C-terminal with Aurora-A (kinase domain). Interestingly, AIBp also interacts with hNinein at the N-terminal, which overlaps with a previously reported hNinein and GSK3beta binding site. Using a kinase assay, AIBp interacts with the Aurora-A kinase domain functions as a positive regulator, whereas AIBp binding to hNinein appears to block the phosphorylation of hNinein by both Aurora-A and GSK3beta. siRNA-mediated elimination of AIBp from HeLa cells, results in a doughnut-like shape, asymmetrical spindle pole and multiple spindle pole formation. We also demonstrated that both AIBp and Aurora-A are co-overexpressed in various brain tumors. These studies demonstrate that AIBp may not only be required for the dynamic movement of Aurora-A at the centrosomes and spindle apparatus during the cell cycle, but may also be important during brain tumorigenesis.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, ROC.
authors.forename: Ann-Shung
authors.initials: AS
authors.lastname: Lieu
authors.forename: Tai-Shan
authors.initials: TS
authors.lastname: Cheng
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Chou
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Wu
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Hsu
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
authors.forename: Joon-Khim
authors.initials: JK
authors.lastname: Loh
authors.forename: Chung-Shing
authors.initials: CS
authors.lastname: Chang
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Hong
mesh_terms: D000595:Amino Acid Sequence; D064127:Aurora Kinases; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D018385:Centrosome / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000502:physiology; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
chemical_list: C553277:AUNIP protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; C512806:NIN protein, human; D009687:Nuclear Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases